ML20147E224
| ML20147E224 | |
| Person / Time | |
|---|---|
| Issue date: | 01/28/1997 |
| From: | Rathbun D NRC OFFICE OF CONGRESSIONAL AFFAIRS (OCA) |
| To: | Gingrich N, Gore A, Murphy R GENERAL ACCOUNTING OFFICE, HOUSE OF REP., SENATE |
| Shared Package | |
| ML20147D933 | List: |
| References | |
| NUDOCS 9702180232 | |
| Download: ML20147E224 (87) | |
Text
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g 1 UNITED STATES j
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[ NUCLEAR REGULATORY COMMISSION
. wasenweron, n.c. men.ses
- January 28, 1997 i The Honorable Al Gore President of the United '
States Senate Washington, DC 20510 j
Dear Mr. President:
i Pursuant to Subtitle E of the Small Business Regulatory Enforcement Fairness l
!- Act of 1996, 5 U.S.C. 801, the Nuclear Regulatory Commission (NRC) is submitting a final rule that amends the Commissions's regulations concerning the criteria for the release of patients administered radioactive material. ,
2 The new criteria for patient release are based on the potential dose to other i individuals exposed to the patient. . The rule is largely in response to three !
l petitions for rulemaking that were submitted by the medical community because !
of concerns that the NRC's recent amendments of its regulations in Part 20, j i- " Standards for Protection Against Radiation," would require medically .
j unnecessary hospitalization of patients administered radioactive materials for l
- the treatment of disease and would thus increase national health care costs. l i The new criteria are consistent with the recommendations of the National i Council on Radiation Protection and Measurements and the International j Commission on Radiological Protection.
We have determined that this rule is not a " major rule" as defined in 5 U.S.C. !
804(2). We have confirmed this determination with the Office of Management i and Budget.
Enclosed is a copy of. the final rule that is being transmitted to the Office of the Federal Register for publication. .The Regulatory Flexibility 1 Certification is included in the final rule. Also enclosed are copies of the Regulatory Analysis and the Environmental Assessment for this rule. This final rule is scheduled to become effective 120 days after publication in the Federal Register. ,
1 Sincerely, fLE#l1 Dennis K. Rathbun, Director Office of Congressional Affairs
Enclosures:
Final Rule ,
Regulatory Analysis '
Environmental Assessment ,
9702180232 970121 PDR ORG NREBRP
l I
l l l l
l l The Honorable Al Gore
! President of the United i States Senate l Washington, DC 20510
Dear Mr. President:
l Pursuant to Subtitle E of the Small Business Regulatory Enforcement Fairness Act of 1996, 5 U.S.C. 801, the Nuclear Regulatory Commission (NRC) is )
, submitting a final rule that amends the Commissions's regulations concerning i the criteria for the release of patients administered radioactive material.
The new criteria for patient release are based on the potential dose to other individuals exposed to the patient. The rule is largely in response to three petitions for rulemaking that were submitted by the medical community because of concerns that the NRC's recent amendments of its regulations in Part 20, i
" Standards for Protection Against Radiation," would require medically unnecessary hospitalization of patients administered radioactive materials for the treatment of disease and would thus increase national health care costs. i The new criteria are consistent with the recommendations of the National l Council on Radiation Protection and Measurements and the International i Commission on Radiological Protection. '
We have determined that this rule is not a " major rule" as defined in 5 U.S.C.
804(2). We have confirmed this determination with the Office of Management and Budget.
Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification is included in the final rule. Also enclosed are copies of the Regulatory Analysis and the Environmental Assessment for this rule. This final rule is scheduled to become effective 120 days after publication in the Federal Register.
Sincerely, l
Dennis K. Rathbun, Director Office of Congressional Affairs j
Enclosures:
Final Rule Regulatory Analysis Environmental Assessment l l
DOCUMENT NAME: G:\SCHNEID\ RELEASE \ LETTERS.FRM.
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OFFICE RPHEB/DRA, , RPHEB/DRA OGC pW -O/RF[ - D/OCA NAME SSchneider hf CTrottier p V)bYskead horris <OhoiM DRathbun f DATE \ ) h97 l /'/97 l /)/97 /d/97 g [h97 / /97 0FFICIAL RECORD COPY f
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pa as:g y *, UNITED STATES g
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NUCLEAR REGULATORY COMMISSION WASHINGTON, D.C. eamma mg "s ,,,, /
e January 28, 1997 l
Mr. Robert P. Murphy General Counsel General Accounting Office !
Room 7175 '
441 G. St., NW Washington, DC 20548 )
Dear Mr. Murphy:
I Pursuant to Subtitle E of the Small Business Regulatory Enforcement Fairness Act of 1996, 5 U.S.C. 801, the Nuclear Regulatory Commission (NRC) is submitting a final rule that amends the Commissions's regulations concerning the criteria for the release of patients administered radioactive material.
The new criteria for patient release are based on the potential dose to other individuals exposed to the patient. The rule is largely in response to three petitions for rulemaking that were submitted by the medical comunity because of concerns that the NRC's recent amendments of its regulations in Part 20, i
" Standards for Protection Against Radiation," would require medically unnecessary hospitalization of patients administered radioactive materials for the treatment of disease and would thus increase national health care costs.
The new criteria are consistent with the recommendations of the National l Council on Radiation Protection and Measurements and the International l Commission on Radiological Protection.
We have determined that this rule is not a " major rule" as defined in 5 U.S.C. i 804(2). We have confirmed this determination with the Office of Management and Budget.
Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification is included in the final rule. Also enclosed are copies of the Regulatory Analysis and the Environmental Assessment for this rule. This final rule is scheduled to become effective 120 days after publication in the Federal Reaister.
Sincerely, z2.Rathbun,Directorx Dennis K shL Office of Congressional Affairs Ev.losures: Final Rule Regulatory Analysis Environmental Assessment
L .
Mr. Robert P. Murphy General Counsel General Accounting Office Room 7175 441 G. St., NW Washington, DC 20548
Dear Mr. Murphy:
Pursuant to Subtitle E of the Small Business Regulatory Enforcement Fairness Act of 1996, 5 U.S.C. 801, the Nuclear Regulatory Commission (NRC) is submitting a final rule that amends the Commissions's regulations concerning .
the criteria for the release of patients administered radioactive material.
.The new criteria for patient release are based on the potential dose to other individuals exposed to the patient. The rule is largely in response to three petitions for rulemaking that were submitted by the medical community because of concerns that the NRC's recent amendments of its regulations in Part 20,
" Standards for_ Protection Against Radiation," would require medically.
unnecessary hospitalization of patients administered radioactive materials for the treatment of disease and would thus increase national health care costs.
The new criteria are consistent with the recommendations of the National Council on Radiation Protection and Measurements and the International Commission on Radiological Protection.
We have determined that this rule is not a " major rule" as defined in 5 U.S.C.
804(2). We have confirmed this determination with the Office of Management and Budget.
Enclosed. is a copy of the final rule that is being transmitted to the Office
'of the Federal Register for publication. The Regulatory Flexibility Certification is included in the final rule. Also enclosed are copies of the Regulatory Analysis and the Environmental Assessment for this rule. This final rule is scheduled to become effective 120 days after publication in the Federal Reaister.
Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs
Enclosures:
Final Rule Regulatory Analysis Environmental- Assessment DOCUMENT NAME: G:\SCHNEID\ RELEASE \ LETTERS.FRM g
- v. .. . .m.un. c.c.. f M b-.e c.,, .n.~.n O.. . u. .
OFFICE RPHEB/DRg RPHEB/DRA ..,0fQ, $h *'"~
MS / D/OCA NAME SSchnei 'CTrottier Wbi skead orris DRathbun DATE }/h7 I/ 397 i /)f97 / hJ/97 k h97 / /97 0FFICIAL RECORD COPf
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j g 1 UNITED STATES
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] NUCLEAR REGULATORY COMMISSION "g g wasmuovow, o.c. saammm i "% * * * * * / Jarnaary 28, 1997 i
b The Honorable Newt Gingrich j Speaker of the United States House of Representatives Washington, DC 20515 4
4
Dear Mr. Speaker:
i j Pursuant to Subtitle E of the Small Business Regulatory Enforcement Fairness i Act of 1996, 5 U.S.C. 801, the Nuclear Regulatory Commission (NRC) is j submitting a final rule that amends the Commissions's regulations concerning
- the criteria for the release of patients administered radioactive material.
The new criteria for patient release are based on the potential dose to other individuals exposed to the patient. The rule is largely in response to three
! petitions for rulemaking that were submitted by the medical community because of concerns that the NRC's recent amendments of its regulations in Part 20, i " Standards for Protection Against Radiation," would require medically j unnecessary hospitalization of patients administered radioactive materials for
- the treatment of disease and would thus increase national health care costs.
- The new criteria are consistent with the recommendations of the National Council on Radiation Protection and Measurements and the International Commission on Radiological Protection.
We have determined that this rule is not a " major rule" as defined in 5 U.S.C.
804(2). We have confirmed this determination with the Office of Management and Budget.
Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification is included in the final rule. Also enclosed are copies of the Regulatory Analysis and the Environnes.tal Assessment for this rule. This final rule is scheduled to become effective 120 days after publication in the Federal Reaister.
I i Sincerely, /
I iwb[ (1- ~
Dennis K. Rathbun, Director Office of Congressional Affairs ;
Enclosures:
Final Rule i Regulatory Analysis Environmental Assessment j i - - , , . -.
t
- l l The Honorable Newt Gingrich l Speaker of the United States l
House of Representatives Washington, DC 20515 i
i I
Dear Mr. Speaker:
r Pursuant to Subtitle E of the Small Business Regulatory Enforcement Fairness- !
Act of 1996, 5 U.S.C. 801, the Nuclear Regulatory Commission (NRC) is !
submitting a final rule that amends the Commissions's regulations concerning the criteria for the release of patients administered radioactive material.
The new criteria for patient release are based on the potential dose to other '
individuals exposed to the patient. The rule is largely in response to three petitions for rulemaking that were submitted by the medical community because of concerns that the NRC's recent amendments of its regulations in hrt 20,
" Standards for Protection Against Radiation," would require medically unnecessary hospitalization of patients administered radioactive materials for the treatment of disease and would thus increase national health care costs.
The new criteria are consistent with the recommendations of the National j Council on Radiation Protection and Measurements and the International Commission on Radiological Protection.
We have determined that this rule is not a " major rule" as defined in 5 U.S.C. ,
804(2). We have confirmed this determination with the Office of Management !
and Budget. ;
Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification is included in the final rule. Also enclosed are copies of the Regulatory Analysis and the Environmental Assessment for this rule. This final rule is scheduled to become effective 120 days after publication in the Federal Reaister.
Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs
Enclosures:
Final Rule Regulatory Analysis Environmental Assessment DOCUMENT NAME: G:\SCHNEID\ RELEASE \ LETTERS.FRM sin.J$Ndb,. c . c.,, .iin .11 n ,.,.noi e,. u . w. ,
OFFICE RPHEB/DRAp RPHEB/DRA , pp C ,, Q4 ,_
JMIEf D/OCA NAME SScttneider k bCTrottier (ph0Imstead korris DRathbun ,
DATE \/[97 I f /97 l /)l97 l (l/97 l k/97 / /97 0FFICIAL RECORD COPY
^*
. o ENVIRONMENTAL ASSESSMENT AND FINDING OF N0 SIGNIFICANT IMPACT 0%
l AMENDMENTS OF 10 CFR PARTS 20 AND 35 ON
" CRITERIA FOR THE RELEASE OF PATIENTS ADMINISTERED RADI0 ACTIVE MATERIAL" Stewart Schneider and Stephen A. McGuire Office of Nuclear Regulatory Research U. S. Nuclear Regulatory Commission
-April 1996
- 1. THE PROPOSED ACTION The Nuclear ' Regulatory Commission (NRC) is amending its regulations in 10 CFR Parts 20 and 35 concerning criteria for the release of patients administered radioactive material. The amendments permit licensees to authorize the release from licensee control of patients administered radiopharmaceuticals or permanent implants only if the dose to total decay to an individual exposed to the released patient is not likely to exceed 5 millisieverts (0.5 rem).
II. NEED FOR THE RULEMAKING ACTION This action is necessary to respond to three petitions for rulemaking.
The petitions were submitted by Dr. Carol S. Marcus, by the American College of Nuclear Medicina (ACNM), and by the American Medical Association (AMA).
NRC's current patient release criteria in 10 CFR 35.75, " Release of Patients or Human Subjects Containing Radiopharmaceuticals or Permanent l Implants," are as follows: "(a) A licensee may not authorize release from confinement for medical care any patient or human research subject .
i administered a radiopharmaceutical until either: (1) The measured dose rate from the patient or human research subject is less than 5 millirems per hour at a distance of one meter; or (2) The activity in the patient or human ,
research subject is less than 30 millicuries; (b) A licensee may not authorize !
release from confinement for medical care of any patient or human research !
l subject administered a permanent implant until the measured dose rate from the l
patient or the human research subject is less than 5 millirems per hour at a distance of one meter " l On May 21,1991 (56 FR 23360), the NRC published a final rule that amended 10 CFR Part 20, " Standards for Protection Against Radiation." The j rule contained a dose limit of 1 millisievert (0.1 rem) (total effective dose i e equivalent) for members of the public in 10 CFR 20.1301(a). When I l 10 CFR part 20 was issued, there was no discussion in the supplemental
\
information on whether or how the provisions of 10 CFR 20.1301 were intended to apply to the release of patients.
Because some licensees were uncertain about what effect the revised 10 CFR Part 20 would have on patient release criteria, three petitions were received on the issue. On June 12, 1991 (56 FR 26945), the NRC published in the Federal Register a notice of receipt of, and request for comment on, a petition for rulemaking (PRM-20-20) from Dr. Carol S. Marcus. The petition requested the NRC to amend the revised Part 20 and 10 CFR 35.75 to raise the annual radiation dose limits to members of the public from'1 milli >Mect -
(0.1 rem) to 5 millisieverts (0.5 rem) from patients administered radioactive materials. In addition, Dr. Marcus submitted a letter dated June 12, 1992, further characterizing her position. On March 9, 1992 (57 FR 8282), the NRC published a notice of receipt and request for comment in the Federal Register for a similar petition for rulemaking (PRM-35-10) from the American College of Nuclear Medicine (ACNM). On May 18,1992 (57 FR 21043), the NRC published in the Federal Register notice of an amendment submitted by the ACNM to its original petition (PRM-35-10A). In addition, the ACNM submitted two letters dated Septer ' r 24, 1991, and October 8, 1991, on the issues in their petition. bn July 26,1994 (59 FR 37950) the NRC published in the Federal Regist_el a petition from the American Medical Association requesting that patient release be regulated by Part 35 rather than Part 20.
On June 15, 1994, the NRC published a proposed rule on criteria for thq release of patients administered radioactive material in response to the petitions (59 FR 30724). The Federal Register Notice for the proposed rule discussed the public comment letters received on the first two petitions.
Three comment letters, each supporting the petition, were received on the third petition (PRM-35-11), but these letters did not contain any additional information not covered by the letters on the first two petitions.
The NRC proposed to amend 10 CFR 20.1301(a)(1) to specifically state that the dose to individual members of the public from a licensed operation does not include doses received by individuals exposed to patients who were released by the licensed operation under the provisions of 10 CFR 35.75. This was to clarify that the Commission's policy is that patient release is governed by 10 CFR 35.75, not 10 CFR 20.1301.
111. ALTERNATIVES CONSIDERED To evaluate the issues raised by the petitioners and the members of the public who commented on the requests made by the petitioners and the proposed rule, the NRC has determined that the following alternatives merit evaluation:
e Alternative 1: 1 millisievert (0.1 rem) total effective dose eauivalent In this alternative, the 1 mil 11 sievert (0.1 rem) per year dose limit in 10 CFR 20.1301(a) it evaluated as the controlling criterion for determining when a patient may be released from the licensee's control.
2
I l
l
- Alternative 2: < 1,110 megabecquerels (30 millicuries) or l
< 0.05 millisievert (5 millirems)/hr at meter In this alternative, the existing patient telease criteria in :
10 CFR 35.75 are evaluated as the controlling requirements for l determining when a patient may be released. l e Alternative 3: 5 millisieverts (0.5 rem) total effective dose eauivalent) '
InthisalternaEive,adoselimitof5millisieverts(0.5 rem)for determining when a patient may be released is evaluated.
The alternatives were evaluated in the regulatory analysis done for the j
rulemaking (Regulatory Analysis on Criteria for the Release of Patients '
Administered Radioactive Materials, Final Report, Stcwart Schneider and Stephen A. McGuire, NRC report NUREG-1492, 1996).
The regula' tory analysis found that there would be no need to retain patients because of any diagnostic procedure under any of the alternatives.
Only about 62,000 therapeutic procedures per year, mostly using iodine-131, would be potentially affected. The costs of the alternatives for the affected therapeutic procedures are presented in Table 1. For details of how the i
results were calculated, the regulatory analysis should be consulted.
Table 1 Annual Attributes of Altematives 1,2, and 3 I
Cost Estimates Hospitalization Value of Records &
Hospital cost lost time Instructions Psychological Collective Retention 8 $ $ cost Dose Alternative (person-rem) (days) (millions) (millions) (millions) (relative) 427,000 427 25.62 O High 1 18,400 29,840 16,000 16 0.96 O Moderate 2
" d O O 2.3 Low 3 ..580 As set forth in more detail in the Regulatory Analysis, Alternative 3 is favored for the following reasons:
- 1. All of the alternatives are acceptable according to generally accepted radiation protection principles, as those expressed by NRC, NCRP, and ICRP, as discussed in Section 4.4 of the Regulatory Analysis.
- 2. Alternative 1 is considerably more expensive to the public compared to Alternative 2 (the status quo) or Alternative 3. Even neglecting the psychological costs, which have not been expressed in dollar terms, the additional cost of Alternative I relative to Alternative 2 is about 3
4 i
$412,000,000 per year, niostly because of increased national health care costs. In view of this, Alternative 1 may be dismissed. ,
- 3. Alternative 3 relative to Alternative 2 has a net value of about Also,
$9,000,000 per year, mostly due to lower health care costs.
Alternative 3 has psychological benefits to patients and their families.
Thus, Alternative 3 is cost-effective in comparison with Alternative 2. 3
- 4. Basing the patient release criteria in 10 CFR 35.75 on the dose to _ , , ~~
individuals exposed to a patient provides a consistent, scientific basis ,
for such decisions that treats all radionuclides on a risk-equivalent basis. The dose delivered by an initial activity of 30 millicuries or a dose rate at 1 meter of 5 millirems per hour varies greatly from one ;
radionuclide to another. Thus, while the values in the current 10 CFR 35.75 may be appropriate for iodine-131, they are too high for some other radionuclides and too low for others.
- 5. A dose-based rule no longer restricts patient release to a specific ;
activity, and therefore would permit the release of patients with ,
activities that are greater than currently allowed. This is especially '
true when case-specific factors are evaluated to more accurately assess the dose to other individuals. For the case of thyroid cancer, in those occasional cases where multiple administrations in a year of i 1,110 millisieverts (30 millicuries) or less of iodine-131 are now administered to a patient, it may be possible to give all of the activity in a single administration. This would reduce the potential for repeated exposures to hospital staff and to those providing care to the released patient. Additionally, this would provide physicians with the flexibility to not have to fractionate doses to avoid ,
hospitalization to meet the current requirements, which may lead to a ,
more effective treatment.
- 6. Shorter hospital stays provide emotional benefits to patients and their families. Allowing c;..' rnnion of families can improve the .
patient's state of mind, which in itself may improve the outcome of the '
treatment and lead to the delivery of more effective health care. !
I i
IV. ENVIRONMENTAL IMPACT 5 0F THE PROPL JD ACTION AND THE ALTE .
Family Members or Other Persons For the purpose of evaluating the environmental impact of the proposed action, the proposed action (Alternative 3) is compared to the impact of the The existing patient release criteria, the status quo (Alternative 2). <
impacts can be seen in Table 1 above. The estimated change in the collective dose when comparing Alternative 3 to Alternative 2 is an increase of about 27 Most of the increase, about 26 i person-sievert (2,700 person-rem).
person-sievert (2,600 person-rem), is received by the primary care-providers :
and family members exposed to released patients (about 10,000) administered )
4 )
l
iodine-131 sodium iodide for thyroid cancer (see Tables 4.10 and 4.11 of NUREG-1492); whereas, 1 person-sievert (100 person-rem) is associated with exposure to released patients (about 1,000) administered more than 1,110 megabecquerels (30 millicuries) of iodine-131 sodium for thyroid Based on the assumption ablation (see Tables 4.10 and 4.11 of NUREG-1492).
that each patient could expose about seven family members and friends (including the primary care-provider), the increase in dose to an affected individual in a year is about 0.00037 sievert (37 millirem) for thyroid cancer and about 0.00014 sievert (14 millirem) for thyroid ablation. T*.e iracan in risk to the affected individual could vary from zerc ('T a<taa threshold exists) to 1.8x10~' per year (if the linear no threshold hypotheses is valid and a risk factor of about 5x10~' per person-rem is used). When compared with the incidence of cancer of 0.20 from natural causes, the potential cancer risk for a family member or other person who has close contact with a thyroid cancer or thyroid ablation patient is small. Thus, the environmental impact is not considered significant.
Breast-feedina Infant There are specific issues associated with the administration of iodine-131 sodium iodide in that following both diagnostic and therapeutic administrations, the dose to a breast-feeding child could exceed 5 millisieverts (0.5 rem) if there was no interruption of breast-feeding. In particular, if the woman does not cease breast-feeding after administration of millicurie quantities of iodine-131 sodium iodide, the internal dose to the breast-feeding infant could be large enough to cause the infant's thyroid to be severely damaged resulting in hypothyroidism. If hypothyroidism were uadiagnosed in very young children, severe mental retardation may occur.
However, if the patient was provided instructions to discontinue breast-feeding, as well as being advised of the consequences of not following the instructions, the NRC believes that the probability of a woman failing to cease breast-feeding after being administered iodine-131 sodium iodide is sa.all . F t .- example, in 1990 an administered dosage of 185 megabecquerels (5 millicuries) of iodine-131 sodium iodide to a patient resulted in her breast-fed infant receiving an unintended radiation dose of 300 grays (30,000 rads) to the infant's thyroid gland. This dose would result in ablation of i the infant's thyroid. This situation was recognized in 2 days which allowed prompt action to be taken thereby reducing potential consequences such as mental retardation. The ARC is aware of two other cases that occurred during 1991 and 1995. In each of these cases, there was a breakdown in communications, rather than lack of intent to prevent breast-feeding.
Although instructions to keep doses to household members and the public as low as is reasonably achieveble are currently required for radiopharmaceutical therapy in 10 CFR 35.315(a)(6), there is no requirement specific to the dose from breast-feeding. In some cases, instructions to 1 interrupt or discontinue breast-feeding may not be effectively communicated.
To deal with this issue, the NRC considered a range of options which varied from maintaining the status quo to the extreme option of a woman remaining in the hospital for a period of time after administration of millicurie quantities of I-131 sodium iodide to ensure her milk prnduction has stopped. l
l l
l l Included within this range of options was the option to enhance communication l
between the licensee and woman regarding instructions to interrupt or l
discontinue breast-feeding before the woman is released from the hospital,
! which is the option adopted in this rulemaki.ng. As discussed in the Regulatory Analysis, the othe- ptions were dismissed as ineffective or impractical due to a variety of reasons: the option of a woman remaining in a l hospital was dismissed due to psychological impacts to the woman and breast-feeding infants, impacts on the practice of medicine, and health carc costs; the option of maintaining status quo was dismissed due to idt.k of assurance that instructions will be provided to a breast-feeding woman. Therefore, the option to enhance communication is selected as the preferred option.
To enhance communications and reduce the probability of a mother breast- !
i feeding after administration of large quantities of iodine-131, amended 10 CFR 35.75(b) will require licensees to provide guidance on the interruption or discontinuation of breast-feeding and information on the rationale for following the guidance. Compliance with the regulation provides NRC with l confidence that the licensee will give the instructions to breast-feeding )
women and it is expected that almost all women will follow instructions to interrupt or discontinue breast-feeding to protect their children from potentially harmful effects. The NRC is not aware of any instances where j instructions were given to the woman but she ignored the warning and continued
' breast-feeding a child. l 1
The decision to require instructions as shown in column 5 of Table B.5 of the Regulatory Analysis (NUREG-1492) is based on both the external and internal dose to the nursing infant. It can be seen from column 4 that for some radiopharmaceuticals the external dose from breast-feeding can be a significant part of the total dose. The duration of the interruption shown in column 6 is selected to reduce the maximum dose to a newborn infant to less than 1 millisievert (0.1 rem). However, the actual doses that would be received by most infants for the recommended interruption periods shown should be a small fraction of 1 millisievert (0.1 rem) due to the conservatism of the analysis. The conservative fa ..rs are basei on. ,'.) the maxilum measured level of activity in breast milk, (2) the longest biological half-life, and (3) the lowest body weight (i.e., the newborn).
It is expected that there will be no effect from breast-feeding on collective dose due to therapeutic administrations, although there may be a small effect from more infants having an opportunity to have contact with a woman sent home from hospital (i.e., cancer patients). However, instructions providing guidance, such as to maintain distance from other persons, should aid in minimizing this effect. In the case of diagnostic administrations of iodine-131 sodium iodide, it is currently normal practice to recommend interruption of breast-feeding. Thus, this rule is expected to have little or no effect on collective dose due to diagnostic administrations, in sum, the environmental impact is not considered significant.
- i. :
i l
l V. FINDING 0F NO SIGNIFICANT IMPACT The Commission has determined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulations in Subpart A of .
10 CFR Part 51, that the amendments are not a major Federal action significantly affecting the quality of the human environment, and therefore an I environmental impact statement is not required. The amendments establish new criteria for patient release that are based on the potential radiation dose to i other individuals exposed to the phi'ic.ct.- Furthermore, the amendments require the licensee to provide written instructions to patients on how to maintain the doses to others as low as is reasonably achievable. It is expected that there will be no significant impact to the environment. ;
VI. LIST OF AGENCIES AND PERSONS CONSULTED The NRC has held public meetings concerning the release criteria for ;
i patients receiving radioactive material for medical use. Appropriate suggestions from the meetings have been incorporated in the proposed amendments. The following table lists the date, location, and the groups ,
represented at each meeting.
Public Meetings Held ;
Date location Groups Represented 07/15/92 Atlanta, GA Agreement States: AL, AR, AZ, CA, 00, FL, 07/16/92 GA, IL, KS, KY, LA, MD, NC, ND, NE, NH, NV, NY, OR, SC, TX, UT, WA, and NY City 10/24/92 Tempe, AZ Agreement States: AL, AR, AZ, CA, CO, FL, GA, IA, IL, KY, LA, MD, MS, NC, ND, NE, 10/25/92 NH, NV, OR, RI, SC, TN, TX, UT, WA, and 10/26/92 10/27/92 NY City 10/24/94 Portland, ME Agreement States: AL, AR, IL, KS, LA, NH, NV, NY, PA, RI, TX, UT, WA, and NY City 10/25/94 Rockville, MD Advisory Committee on the Medical Uses of 10/22/92 Isotopes (ACMUI) 10/23/92 05/03/93 Bethesda, MD Advisory Committee on the Medical Uses of ,
05/04/93 Isotopes (ACMUI) l Reston, VA Advisory Committee on the Medical Uses of I 11/01/93 l Isotopes (ACMUI)
Rockville, MD Advisory Committee on the Medical Uses of 11/18/94 Isotopes (ACMUI) l 05/12/95 Rockville, MD Advisory Committee on the Medical Uses of Isotopes (ACMUI) 7 l
! i l l l .
i i
10/18/95 Rockville, MD Advisory Committee on the Medical Uses of ,
10/19/95 Isotopes (ACMUI) 4 Much of the statistical and techaical information required for this -
assessment is not available in the open literature. In such instances, r
information was obtained directly from technical experts. The following l
individuals are acknowledged for their cooperation and contribution of technical information and dat.. -
r R. Atcher, Ph.D., Radiation and Cellular Oncology Department, University >
l l of Chicago, Chicago, IL K. Behling, S. Cohen and Associates, McLean, VA ,
U. H. Behling, S. Cohen and Associates, McLean, VA t D. Flynn, M.D. (NRC Advisory Committee on Medical Use of Isotopes),
Massachusetts General Hospital, Boston, MA l D. Goldin, S. Cohen and Associates, McLean, VA .
f W.R. Hendee, Ph.D., Dean of Research, Medical College of Wisconsin, :
Milwaukee, WI :
P. Holahan, Ph.D., U.S. Nuclear Regulatory Commission, Washington, DC C. Jacobs, President, Theragenics, Norcross, GA F. A. Mettler, M.D., Department of Radiology, University of New Mexico, School of Medicine, Albuquerque, NM K.L. Miller, CHP, Professor of Radiology and Director, Division of Health Phytics, Milton Hershey Medichl Center, Hershey, PA R. Nath, Ph.D., Professor of Yale University, School of Medicine, and past President of the American Association of Physicists in Medicine, New Haven, CT M.P. Nunno, Ph.D., CHP, Cooper Hospital, University Medical Cen'.er, Camden, NJ P. Paras, Ph.D., Food and Drug Administration, Center for Devices and Radiology Health, Rockville, MD M. Pollycove, M.D., Visiting Medical Fellow, U.S. Nuclear Regulatory Commission, Washington, DC l-G.E. Powers, Ph.D., Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 8
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M. Rosenstein, Ph.D., Food and Drug Administration, Center for Devices and Radiology Health, Rockville, MD J. St.Germain, Radiation Safety Officer, Memorial Sloan Kettering, New .
York City, NY B.A. Siegel, M.D. (Chairman, NRC Advisory Committee on Medical Use of Isotopes), Director, Division.of Nuclear Medicine, Mallinckrodt Institu+a af. Badiology, Washington University Medical Center, St. Louis, M0 l
M.G. Stabin, Ph.D., CHP, Radiation Internal Dose Information Center, Oak Ridge Institute for Science and Education, Oak Ridge, TN I
D. Steidley, Ph.D., CHP, Medical Health Physicist, Department of Oncology, St. Barnabas Medical Center, Livingston, NJ \
J. Stubbs, Ph.D., Radiation Internal Dose Information Center, Oak Ridge l Institute for Science and Education, Oak Ridge, TN l K. Suphanpharian, Ph.D., President, Best Industries, Springfield, VA R.E. Toohey, Ph.D., Director, Radiation Internal Dose Information Center, Oak Ridge Institute for Science and Education, Oak Ridge, TN j i
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9 ,
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t NRC REVISES REGULATIONS ON RELEASE ,
0F PATIENTS ADMINISTERED BYPRODUCT MATERIAL l
The Nuclear Regulatory Commission is amending its regulations governing the release of patients from a hospital or other licensed medical facil.ity _.
after they have received radioactive material for treatment or diagnostic purposes. The revisions respond to three petitions received on this subject. .
1 Radioactive pharmaceuticals or radioactive implants are administered to approximately 8 to 9 million patients in the United States each year for diagnosis or treatment of disease. These patients can expose other persons ;
around them to radiation until the radioactive material has been excreted from l their bodies or has become less intense due to radioactive decay.
Under the final rule, licensees may not authorize the release of patients if the estimated dose, to anyone in contact with the patient, would be greater than 500 millirems. (Typical natural background radiation in the United States is 309 millirems per year.) The new criteria are consistent with recommendations of the International Commission on Radiological Protection and the National Council on Radiation Protection and Measurements.
Under current NRC medical use regulations, licensees are not permitted to authorize the release of patients to whom nuclear material has been administered until either (1) the measured dose rate from the patient is less than 5 millirems per hour at a distance of 1 meter or (2) the radiopharmaceutical content of the patient is less than 30 millicuries.
The final rule amends the NRC's general radiation protection regulations :
to exclude doses to individuals exposed to released patients. Release of patients containing radioactivity is instead governed by the more explicit 1
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requirements of~ revised medical use regulations, which include, in addition to 1 the 500-millirem limit, a requirement that, if the dose to an individual l exposed to the patient is likely to exceed 100 millirems, the licensee must ;
provide the patient with written instructions on how to minimize exposures to l
others. If the released individual may be breast-feeding an infant or child, the instructions must also include guidance on the interruption or. ' ~~
i discontinuation of breast-feeding and information on the consequences of ;
i l failure to follow the guidance. l l
The revisions partially grant three petitions for rulemaking on criteria ]
for release of patients who have been administered radioactive material. On i i
l June 12, 1991, March 9, 1992, May 18, 1992, and July 26, 1994, the NRC j l
published Federal Register notices concerning receipt of the petitions from ,
1 Dr. Carol S. Marcus, the American College of Nuclear Medicine and the American l I
l l Medical Association. )
A proposed rule on this subject was published in the Federal Register on June 15, 1994. The final rule reflects public comments received.
The rule will be effective (120 days after publication of a Federal L, ratice or ).
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i j NUREG-1492
! Regulatory Ana:ysis on-Criteria 3
for the Release of Patients Administerec. Racioactive Materia ~
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. Fina Report i ,
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U.S. Nuclear Regulatory Commission l l
Office of Nuclear Regulatory Research S. Schneider, S. A. McGuire p massyy 4.e,/%,.41..
NUREG-1492 Regulatory Analysis on Criteria ~ ~
for the Release of Patients Ac ministered Radioactive Material Final Report Manuscript Completed: April 1996 Date Published: February 1997 i S. S'.hneider, S. A. McGuire Division of Regulatory Applications Omce of Nuclear Regulatory Research U.S. Nuclear Regulatory Commission Washington, DC 20555-0001 i
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1 <*- l I: l ABSTRACT !
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I The Nuclear Regulatory Contmission (NRC) has The evaluation demonstrates that diagnostic !
j received three petitions to amend its regulations procedures ue unaffected by the choice of l in 10 CFR Parts 20 and 35 as they apply to doses alternative. Only some therapeutic l l !
! received by members of the public exposed to administrations of radioactive material could be j patients released from a hospital aun they have affected by the choice of alternative. The ~ ~~
been administered radioactive material. While the evaluation indicates that Alternative I would cause !
three petitions are not identical, they all reqgt !
1 a large increase in the national health care cost t
] that the NRC establish a dose limit of 5 milhueveJs because of longer hosp. ital stays and would cause 6 l
j (0.5 rem) per year for .individuals exposed to patien's 5 8 cant Personal and psycholog.ical costs to l
! who have been administered radioactive ma"..ials. Patients and the,ri famih,es. The choice of ,
This regulatory analysis evaluates three altunatives. Alternative 2 or 3 would affect only thyro,d i cancer Alternative 1 is for the NRC to amend it, patient !
patients and some hyperthyroid patients treated release criteria in 10 CFR 35.75 to use tne more with iodine-131. For those patients, Alternative 3 l stringent dose limit of 1 millisievert (0.1 rem) per j would result in less hospitalization than year in 10 CFR 20.1301(a) for its patient release criteria. Alte: native 2 is for the NRC to continue Alternative 2. Alternative 3 could decrease j national health care costs by $13,700,000 per year j using the existing release criteria in 10 CFR 35.75 of 1,110 megabecquerels (30 millicuries) of activity btt would increase the potential collective dose
- o. 4 doe rate at 1 meter from ti.e patient of 0.05 milli. from released therapy patients by about - l 2,740 person-rem per year, mainly to family j sievert (5 millirems) per hour. Alternative 3 is for the NRC to amend the patient release criteria in members. Alternative 3 would also have personal l 10 CCR 35.75 to specify a dose limit of and psychological benefits for the patients and '
5 millisieverts (0.5 rem) for patient release. their families.
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iii NUREG-1492
CONTENTS .
ABSTRACT . . . . . . . . . ................................... . . . . . . . . . . . . . . . . . . . . iii ACKNOWLEDGEMENTS .................. ....................................ix 1
1 STATEMENT OF THE PROBLEM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 OBJECTIVES OF THE RULEMAKING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 l 3 ALTE RNATIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 4 CO NS EQUENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1 4.1 Current Uses of Radiopharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ]
4.1.1 Diagnostic Administrations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 !
4.1.1.1 Estimates of the Number of Diagnostic Procedures Performed . . . . . . . . . . . . . . 3 4.1.1.2 Age and Sex Distribution of Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 4.1.2 Therapeutic Administrations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 i 1
4.1.2.1 Radiopharmaceuticals Used in Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 4.1.2.2 Radioactive Materials Used in Permanent implants (Brachytherapy) . . . . . . . . . 9 4.1.2.3 Summary of Therapeutic Administrations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 l
4.2 Assessment of Doses to Individuals Exposed to Patients Administered Radioactive 10 Materials ..............................................................
i 10 4.2.1 Methodology for Calculating External Gamma Dose . . .. . . . . . . . . . . . . . . . . . . . . . . . .
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4.2.1.1 O ccu pancy Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 4.2.1.2 Exposure Rate Constant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 4.2.1.3 Biological Retention and Elimination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 4.2.1.4 Tissue Shielding for Permanent implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 4.2.2 Assessment of Internal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .... 14 l 14 4.2.2.1 Internal Exposure Pathways . . . . . . . . . . . . . . . . . . . . . . ... .. ..... ... ,
4.2.2.2 Measurements of Internal Exposure . . ........... . ........ ...... 15 l 4.2.3 Estimate of Maximum Likely Doses to Individuals Exposed to Patients . .... .... . 16 i
4.2.3.1 Diagnostic Procedures . . . . . . ... . . ..................... ...... 16 16 4.2.3.2 Therapeutic Procedures . . ............ ... . ...... ... .... .
4.2.4 Assessment of Doses to Breast-Feeding infants . . . . . . ............ . .. 16 19 4.2.4.1 Internal Dose . ... ... .. .... .... ..... .. .. . ...
19 4.2.4.2 External Dose . . . ... . . ... . . . . . . ;
19 4.2.4.3 Special Considerations for lodine-131 Sodium Iodide .. . , . .
4.2.4.4 Summary of Doses to Breast-Fuiing InSnts . . . . 20 v NUREG-1492
21 4.2.5 Collective Dose . . . . . . ................... .......... . ..... . . . . . .
21 4.2.5.1 Collective Dose to Individuals . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . .
4.2.5.2 Collective Dose to Breast-Feeding Infants . . . . . . . .................24 24 43 Value impact Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
24 43.1 Estimates of the Potential Costs . . . . . . . . . . . . .............................
43.1.1 Estimates of the Direct Costs of Patient Retention . . . . . . . . . . . . . . . . . . . . . . 24 26 43.1.2 Derivation of Indirect Costs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . .
43.13 Evaluation of Psychological Costs . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . 27 27 43.2 Costs and Benefits of Alternatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.4 Evaluation of the Alternatives With Respect to Accepted Radiation Protection 28 Prin ciples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
28 5 DECISION RATIONALE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6 IM PLEM ENTATION . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 30 7 REFERENCES. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
APPENDIX A . Parameters and Calculations for Determining Release Ouantities and Dose Rates for Radionuclides Used in Medicine ....... ..................A.1 APPENDIX B - Parameters and Calculations for Determining Instructions to Breast. Feeding Women..........................................................B.1~
B.1 Calculational Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B.1 B .2 R esult s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . B .2 .
B.2.1 Biokinetic Data for Excretion of Radiopharmaceuticals in Breast Milk . . . . . . . . . . . . B.2 B.2.2 Radiation Dose Estimates . . . . . . . . . . . . . . . . . . ...........................B3
....... ..... . B.25 B3 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Tables 4.1 Estimated Number of Diagnostic Radiopharmaceutical Procedures Performed in the United States Between 1972 and 1982 . . . . . . . . . . . . . .. . . ... .. . . .......4 4.2 Estimated Radiopharmaceutical Use for Diagnostic Procedures in the United States in 1993 . . 5
..... .. 6 43 Age and Sex Distribution of Patients 11aving Nuclear Medicine Examinations . .
4.4 Number of Annual Therapeutic Administrations in the U.S. (significant gamma. emitting
. . . 11 radionuclides only) ... ..... .. .. .. . . .. . .
N U R EG-1492 vi
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-I 4.5 Family Doses from Patients Treated with lodine.131 for Thyroid Carcinoma . . . . . . . . . . . . . 12 r 4.6 lodine-131 Biological Retention and Elimination Parameters for Hyperthyroidism, Thyroid ,
Ablation, and Thyroid Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......... 14 4.7 Maximum Likely Doses to Total Decay to Exposed Individuals from Diagnostic Procedures . . 17 Maximum Likely Doses to Total Decay to Exposed Individuals from Therapeutic Procedures ;
4.8 Assuming No Hospitalization . . . . . . . . . . J'. ; . . . . . . . : : ; . . . . . . . ................ 18 !
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[- 4.9 Estimates of Collective Dose from Therapeutic Radioiodine Procedures for Alternative 1:
Annual Limit of 1 millisievert (0.1 rem) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 4.10 Estimates of Collective Dose from Therapeutic Radioiodine Procedures for Alternative 2:
l Limit of 1,110 megabecquerels (30 millicuries) or 0.05 millisievert (5 millirems)/hr . . . . . . . . 22 j 4.11 Estimates of Collective Dose from Therapeutic Radioiodine Procedures for Alternative 3: !
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Annual Limit of 5 millisieverts (0.5 rem) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.12 Duration of Retention per Therapeutic Procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 4.13 Annual Attributes of Alternatives 1, 2, and 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 i
l 4.14 Annual Costs and Benefits of Alternatives 1 and 3 Compared to Alternative 2 28 (Th e Stat us Q uo) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
A.1 Helf. Lives and Exposure Rate Constants of Radionuclides Used in Medicine . , . . . . . . . . . . . A.1 ,
A.2 Calculations of Exposure Rate Factors, Release Quantities, and Release Dose Rates . . . . . . . A.3 B.1 Effective Dose Equivalents to Newborns and One-Year. Olds from infant's Intake of R adiopharm a ce uticals . . . . . . . . . . .. . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B.4 II.2 Excro '.cn Practions and Biological Half. Lives for Radiopharmaceuticals Excreted in B reast M ilk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B .5 B.3 Biological and Physical Parameters Used to Calculate the Total Activity ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk . . B.8 B.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules . . . . . . . . . B.10 B.5 Potential Doses to Breast. Feeding infants from Radiopharmaceuticals Administered to a Woman if No Interruption of Breast.Feedinr and Recommendations on Interruption
. ............ B.23 of Breast Feeding . . . . . . . . . . . . .. .. . .. . . ...
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i ACKNOWLEDGEMENTS ;
i Much of the statistical and technical information P. Paras, Ph.D., Food and Drug . t required for this analysis is not available L . e Administration, Center for Devices and open literature. In such instances, information Radiology Health, Rockville, MD l was obtained directly from technical experts. The following individuals, are acknowledged for their . M. Pollycove, M.D., Visiting Medical .
cooperation and contribution of technical Fellow, U.S. Nuclear Regulatory information and data. Commission, Washington, DC R.. Atcher, Ph.D., Radiation and Cellular G.E. Powers, Ph.D., Office of Nuclear ,
Oncology Department., University of Regulatory Research, U.S. Nuclear :
Chicago, Chicago, IL Regulatory Commission, Washington, DC !
K. Behling, S. Cohen and Associates, McLean, VA M. Rosenstein, Ph.D., Food and Drug Administration, Center for Devices and j U. H. Behling, S. Cohen and Associates, Radiology Health, Rockville, MD j McLean, VA J. St.Germain, Radiation Safety Officer, D. Flynn, M.D. (NRC Advisory Committee Memorial Sloan Kettering, New York City, NY on Medical Use of Isotopes), Massachusetts General Hospital, Boston, MA B.A. Siegel, M.D., (Chairman, NRC
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D. Goldin, S. Cohen and Associates, Isotopes) Director, Dmston of Nuclear
- ""' ^ Medicine, Mallinckrodt lastitute of adiology, Washington Unimsity Md W.R. Hendec, Ph.D., Dean of Research, Center, St. km,s, MO Medical College of Wisconsin,;.lilwaukee, WI P. Holahan, Ph.D., U.S. Nuclear Regulatory M.G. Stabin, Ph.D., CHP, Radiation Internal Dose Information Center, Oak Commission, Washington, DC Ri. . ;titute for Scit .ce and Education, C. Jacobs, President, Theragenics, Oak Ridge, TN Norcross, GA D. Steidley, Ph.D., CHP, Medical Health F.A. Mettler, M.D., Department of Physicist, Department of Oncology, St.
Radiology, University of New Mexico, Barnabas Medical Center, Livingston, NJ School of Medicine, Albuquerque, NM J. Stubbs, Ph.D., Radiation Internal Dose K.L. Miller, CHP, Professor of Radiology Information Center, Oak Ridge Institute for and Director, Dm,ston of Health Phys,ics, Science and Education, Oak Ridge, TN Milton Hershey Medical Center, Hershey, PA K. Suphanpharian, Ph.D., President, Best R. Nath, Ph.D., Professor of Yale Industries, Springfield, VA University, School of Medicine, and President of the American Association of !
Nuclear Physics, New Haven, CT R.E. Toohey, Ph.D., CHP, Director, '
Radiation Internal Dose Information '
M.P. Nunno, Ph.D., CHP, Cooper Hospital, Center, Oak Ridge Institute for Science and University Medical Center, Camden. NJ Education, Oak Ridge, TN l
ix NUREG-1492
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1 STATEMENT OF THE _ submitted by Dr. Carol s. Marcus (PRM-=20, 56 FR 26945), requested that the NRC:
PROBLEM (1) Raise the annual radiation dose lima in 10 CFR 20.1301(a) for individuals exposed to radiation from patients receiving radiopharma-Each year in the United States, radioactive ceuticals for diagnosis or therapy from 1 milli-pharmaceuticals or compounds or radioactive implants are administered to rouqhly 8 to sievert (0.1 rem) to 5 millisieverts (0.5 rem).
l 9 million patients for the diagnosis or treatment
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of disease. These people can expose others (2) Amend 10 CFR 35.75(a)(2) to retain the ;
1,110-megabecquerel (30-mi!Iicurie) limit for around them to radiation until the radioactive i dine-131 (I-131), but provide an activity material has been excreted from their bodies or limit for other radionuclides consistent with has decayed away.
the calculational methodology employed in i NRC's patient release criteria in 10 CFR 35.75, and Measurements (NCRP) Report No. 37,
- Release of Patients or Human Research Subjects anagemem of Padeds recaW2 ns in c Containing Radiopharmaceuticals or Permanent Who Have Rece@ived Therapeutic Amounts o 1 I
implants,, are as follows:
Radionuclides" (NCRP70).
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(a) A licensee may not authorize release from (3) Delete 10 CFR 20.1301(d), which requires I confinement for medical care any patient or licensees to comply with provisions of EPA's human research subject administered a env ronmental regulations in 40 CFR Part 190 radiopharmaceutical until either: (1) The in addition to complying with the requirements measured dose rate from the patient or the of 10 CFR Part 20.
human research subject is less than 5 millirems per hour at a distance of 1 meter; The second petition, submitted by the American l
or (2) The activity in the patient or the College of Nuclear Medicine (ACNM) (PRM-35-10, human research subject is less than 57 FR 8282, as revised by PRM-35-10A, l 30 millicuries; (b) A licensee may not 57 FR 21043), requested that the NRC:
i authorize release from confinement for medical care of any patient or human '1)
Adopt a dose limit o* $ millisleverts (0.5 rem) l research subject administered a permanent for individuals exposed to patients who have implant until the 'neasured dose rate fmr" been administered radiopharmaceuticals.
l the patient or the human research subject is less than 5 millirems per hour at a distance of (2) Permit licensees to authorize release from 1 meter." hospitalization any patient administered a '
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! radiopharmaceutical even if the activity in the On May 21,1991, the NRC published a final rule patient is greater than 1,110 megabecquerels that amended 10 CFR Part 20," Standards for (30 millicuries) by defining " confinement
- to Protection Against Radiation" (56 FR 23360). include confinement in a private residence.
The rule contained limits on the radiation dose for members of the public in 10 CFR 20.1301. A third petition (PRM-35-11,59 FR 37950) l However, when 10 CFR Part 20 was issued, there dealing, in part, with these same issues was submitted ;
by the American Medical Association (AMA).
was no discussion in the supplemental information on whether or how the provisions of 10 CFR 20.1301 The main point of the petition is that the were intended to apply to the release of patients, radiation dose limits in 10 CFR 20.1301 should thereby creating the need to address this issue. not apply to individuals exposed to the patient.
i Uccause some licensees were uncertain what effect Since the petitions submitted by Dr. Marcus, the the revised 10 CFR Part 20 would have on patient ACNM, and the AMA all address the patient release criteria, three petitions for rulemaking release criteria in 10 CFR 35.75, the NRC decided were received on this issue. The first petition, to resolve these petitions in a single rulemaking. !
1 NURIE 1492
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controlling requirements for determining 2 OBJECTIVE OF THE when a pati ent may be released from the RULEMAKING hcensee's control. ,
o Alternative 3: 5 millisieverts (0.5 rem) total effective dose eavivalent The objective of this rulemaking is to respond to the three petitions for rulemaking by amending, as This alternative evaluates a dose limit of deemed e ' r.315 the patient release criteria in 5 millisieverts (0.5 rem) to an individual 10 CFR 3U5. -
- - ::: posed to a patient as the limiting factor for determining when a patient may be released from the licensee's control.
3 ALTERNATIVES 4 CONSEQUENCES As the petitions and the public comments that were submitted to the Commission on the petitions made clear, some licensees were To evaluate the impacts of the three alternatives, uncertain about whether dose limits imposed by it is necessary to determine which current 10 CFR 20.1301(a) or the patient release criteria procedures involving the administration of established by 10 CFR 35.75 govern patient radiopharmaceuticals or permanent implants release. In the Commission's view,10 CFR 35.75 might be affected by the imposition of a dose governs patient release as explained in the Notice limit of 1-millislevert (0.1-rem) total effective dose of Proposed Rulemaking (59 FR 30724). The equivalent for individuals exposed to released public comments received on the three petitions patients. For convenience, procedures involving and on the Notice of Proposed Rulemaking also the administration of radioactive materials to made it clear that the majority of commenters patients may be classified as: (1) diagnostic i favored an annual dose limit of 5 millisleverts procedures involving administration of (0.5 rem). Given that 10 CFR Part 35 was radiopharmaceuticals to obtain information about deemed to be the controlling regulation, the normal and pathological processes in the patient; Commission was faced with the decision regarding or, (2) therapeutic procedures involving i l
the regulatory approach to be pursued in administration of radiopharmaceuticals or 10 Ct-K 35.75. To evasuate the issues raised by implantation of a radioactive source to destroy i the petitioners and those who commented on the diseased tissue in the patient.
requests made by the petitioners and the Notice of Proposed Rulemaking, the NRC determined that the following alternatives should be evaluated: 4.1 Current Uses of i e Alternative 1: 1 millisievert (0.1 rem) total Radiopharmaceuticals I effective dose eauivalent Radiopharmaceuticals can be defined as " drugs" This alternative evaluates a dose limit of that are radioactive. Although radiopharma-ceuticals, diagnostic or therapeutic, may be 1 millisievert (0.1 rem) to an individual exposed to a patient as the limiting factor for classified as drugs,it should be noted that determining when a patient may be released radiopharmaceuticals are not given for the .
purpose to exert any pharmacological action. !
from the licensee's control. l e Alternative 2: < 1.110 menabecouerels Radiopharmaceuticals are generated from two 00 millicuries) or < 0.05 millisievert sources: nuclear reactors and accelerators.
(5 millirems)/hr at 1 meter Nuclear reactors can produce radionuclides i through neutron capture reactions (e.g., (n, y), f in this alternative, the current patient release (n, p), and (n, a)), as well as by nuclear fission criteria in 10 CFR 35.75 are evaluated as the (n. f). Other radiopharmaceuticals are accelerator i NU R EG.1492 2 ,
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l l .
produced, in which a highly pure target material is RED 2 studies) (ME85). The RED 1 study bombarded with protons, deuterons, or alpha examined the computer billing records of particles. Many have relatively short half lives. 81 hospitals. Data for the subsequ,ent RED 2 Some radiopharmaceuticals may be produced by study reflect information obtained by mail survey either reactor or accelerator (e.g., palladium-103 from 500 hospitals.
(Pd-103) and iodine-125 (I-125)). The choice in production method is dictated by cost Data for 1982 were also provided by Parker, et al.
_ _ considerations and vendor access to a high (PA84) in which a randomized sample of neutron flux reactor facility. ' While most 10 percent of the U.S. hospitals were surveyed.
iodine-125 has in ac & .a.d antinues to be Although his survey was specifically directed to produced by reactors, the production of thyroid examinations, survey data also provided palladium-103 has shifted from reactor t estimates of total examinations.
accelerator (personal communication, C. Jacobs, August 1993).
All of the studies mentioned above are summarized in Table 4.1 and represent hospital 4.1.1 Diagnostic Administrations data only. However, the exclusion of non-hospital facilides should not significantly affect the 4.1.1.1 Estimates of the Number of Diagnostic accuracy of estimates since less than 1 percent of Procedures Performed all nuclear medicme procedures are performed utside hospitals (JO83). Inspection of Table 4.1 Estimates regarding the frequency and total reveals severtiimportant trends. While the total number of diagnostic nuclear medicine procedures nuruber i diagnostic procedures has shown a have been reported over the years in several generalincrease, the number of specific studies reviewed and analyzed by Mettler, et al. pr cedures has in some cases dramatically (ME85). Among the earliest data reported was a mereased or decreased. By 1982, there were ,
study supported by the American College of ***' radionuclide brain imaging examinations Radiology (ACR75), which reflects data collected than.m 1972, undoubtedly due to replacement by in 1972 by J. Lloyd Johnson Associates. comPutertzed tomography (ME85). For the same Additional data for the years 1973 and 1975 were ,
peri d, liver imagmg mereased tenfold. The obtained in a similar fashion and also published in
!*'8*st percent increase involves cardiovascular the American College of Radiology Manpower .
tmagmg, which increased from an estimated ,
Survey (ACR82). 25,000 procedures in 1972 to about 950,000 in {
1982. Other procedures such as renal, lung, and In 1975, the Bureau of Radiological Heahh tumor unagmg have experienced only modest (BRH; now the Center for Medical Devices and increases in numbers.
Radiological Health, CDRH) of the United States Foul and Drug Administration initiated a pilot A search of the open literature revealed no recent study that surveyed information reported by six comprehensive studies to assess more current U.S, hospitals to the Medically Oriented Data System use of radiopharmaceuticals. It is generally ,
(MODS). This project was later expanded to '
include 26 stratified hospitals that provided data thought, however, that the frequency and usage of radiopharmaceuticals have stabilized because of for 1977 and 1978 (FDA85).
the competing technologies of computerized tomography, magnetic resonance knaging, and Comprehensive data on 1980 diagnostic imaging ,
gray-scale ultrasound (personal communication, procedures were obtained by J. Lloyd Johnson F.A. Mettler, March 1993). For this report, the Associates by mail questionnaire using a stratified most recent RED 2 frequency distribution and the random sample of general hospitals and selected cumulative frequency of 16 diagnostic nuclear office practices in the U.S. (JO83). The sample included 6,1W hospitals and was estimated to medicine procedures per one-thousand population will be used to estimate current usage. Table 4.2 reflect about 90 percent of the total diagnostic imaging examinations. Additional studies were provides frequency estimates of diagnostic l procedures adjusted to reflect the 1993 U.S.
conducted by the BRH for the years 1980,1981, and 1982. The hospital-based survey was called population, which it projected at 256,466,000 by the Radiation Experience Data (RED 1 and the United States Bureau of the Census.
3 NU REG.1492
l l
l
. . . l l
Table 4.1 Estimated Number of Diagnostic Radiopharmaceutl cal Procedures Performed in the l United States tietween 1972 and 1982 Year i i
1972 1973 1975 1978 1980 1980 1981 1982 1982 Source l 1
Examination ACR ACR ACR MODS Johnson RED 1 RED 2 RED 2 Parker Type _
Brain 1260m 1510 2120 1546 870 1176 1038 812 -
Hepatobiliary 26 --- --- --- --- --- 109 179 --
Liver 455 535 676 1302 1180 1399 1445 1424 -
Bone 81 125 220 1160 1270 1307 1613 1811 -
Respiratory 332 417 597 1053 830 898 1095 1191 -
i 460 627 699 650 506 664 677 533 Thyroid 356 Urinary 108 122 154 205 200 164 402 236 --
22 166 130 125 121 ---
rumor 10 14 ---
Cardiovascular 25 33 49 160 58G 558 708 950 ---
i Other 686 294 338 120 120 368 - --- ---
4803 6411 5830 6374 7199 7401 7690 Total 3339 3510 (16)S (17) (22) (29) (26) (28) (31) (32) (33) source: ME85.
"' Numbers not in parenthesis indicate number of examinations x 1,000.
- Numbers in parenthesis indicate number of examinations /1,000 population.
The identity, chemical form, and typical quantity 3 percent use iodine-131 or iodine-123 (1-123),
administered of radionuclides used for diagnostic and about 2 percent use gallium-67 (Ga-67),
in-vivo procedures are cited in Table 4.2 and reflect values cited by Mettler, et al. (ME86). 4.1.1.2 Age and Sex Distribution of Patients It can be assumed that the typical quantity per examination has not significantly changed since the time of original publication (personal The age and sex distribution of the United States communication, F.A. Mettler, March 1993). population that underwent nuclear medicine examinations in 1980, as cited by Mettler, et al.
As the results in Table 4.2 indicate, there are (ME86), is shown in Table 4.3. For the period of approximately 8.2 million diagnostic examinations observation, more than three-fourths of all nuclear employing radiopharmaceuticals performed medicine examinations were performed on annually in the United States. Of these, more than persons over the age of 45; nearly 40 percent of 85 percent use technetium-99m (Tc-99m) as the these patients were 64 years and older. With the label, about 5 percent use xenon 133 (Xc-133), exception of the youngest age category, the about 5 percent use thallium 201 (TI-201), about percentage of females exceeded males.
NilR EG- 1492 4
, l l l 1
\
Table 4.2 Estimated Radiopharmaceutical Use for Diagnostic Procedures in the l
United States in 1993* I i
! Typical Activity Number of !
Examination Type per Extmination Examinations (Radiopharmaceutical) (MBq) (mCl) (x 1,000) l l Brain j - Tc-99m DTPA 740 (20) 450 l
-740- (20)..- 450 l
- Tc-99m O. (Pertechnetate) 1 Hepatobiliary
- Tc-99m IDA 185 (5) 198 Liver i
- Tc-99m Sulfur Colloid 185 (5) 1,578 l Bone
- Tc-99m Phosphate 740 (20) 2,007 Lune Perfusion
- Tc-99m MAA 185 (5) 871 1
Lune Ventilation
- Xe-133 370 (10) 449 i
Thyroid 185 (5) 600
- Tc-99m O. (Pertechnetate)
- I-123 11.1 (0.3) 75 I-131 3.7 (0.1) 75 l l
Renal j
- Tc-99m DTPA 740 (20) 157 l
- I 131 Hippuran 9.3 (0.25) 105 Cardiovascular
- Tc-99m RBC 740 (20) 421 Tc-99m Phosphate 740 (20) 211 l
- TI-201 Chloride 111 (3) 421 l Tumor
- G: 57 Citrate 111 (3) 134 Total 8,202
'" Based on ME86; and personal communication, F. A. Mettler, March 1993, but adjusted for the 1993 United States population. ,
I I
I l
l l
l 5 NUR EG-1492
, i Table 4.3 Age and Sex Distribution of Patients Itaving Nuclear Medicine Examinations Male Female Total Age (%) (%) (%)
< 15 0.9 0.7 1.6 15 - 29 3.3 4.9 8.2 30 - 44 5.2 8.7 13.9 45 - 64 15.8 21.6 37.4
> 64 17.0 21.9 38.9 Source: ME86.
is most commonly associated with Graves' 4.1.2 Therapeutic Administrations Disease. Graves' Disease is an autoimmune disease in which the body's own immune system is Therapeutic tise of radioactive materials involves directed against cellular and secretary products of two distinct approaches. The first involves the the thyroid gland. Hyperthyroidism can also be oral, intravenous, or intracavity administration of the result of excessive hormone production by a a radiopharmaceutical that may subsequently be single " toxic" nodule, thyroid carcinomas, and distributed, concentrated, retained, and climinated medications inclusive of potassium iodide.
by physical, chemical, and metabolic actions occurring within the body. The second approach . .
liyPerthyro.d.i tsm is not a condition reportable to involves the implantation of radioactive sources public health agencies. As a result, data on rates (i.e., seeds) directly into a solid tumor. While f ccurrence and treatment must be inferred.
both temporary and permanent implants are incidence of hyperthyroidism is reported at 3 per performed, all patients receiving temporary 10,000 adults per year, with peak tacidence implants are hospitalized until the implants are ccurring between 30 and 50 years of arte (DG79).
removed. Thus, only permanent implants are potentially affected by this rulemaking. From the most recent data (1990) available from the United States Bureau of the Census,it can be 4.1.2.1 Radiopharmaceuticals Used in 'Dierapy assumed that about 75 percent of the United States population (approximately 191,500,000 '
The in-vivo use of radiopharmaceuticals in therapy persons) is 18 years of age or older. Thus, it can is based on the ability to differentially deliver be estimated that about 57,500 individuals per i lethal radiation doses to the selected target tissue. year require medical treatment for l Most desirable are beta emitters that can deliver hyperthyroidism. 1 j
intense irradiation of target cells while sparing the surrounding tissues. In contrast to diagnostic Although medical treatment may in some cases l procedures for which the gamma emission is involve the use of anti-thyroid drugs or surgery, it essential, the emission of energetic gammas is may be assumed that about 85 percent of the undesirable for therapeutic purposes since it cases of hyperthyroidism are treated with results in unwanted irradiation of surrounding therapeutic doses of iodine-131 (personal healthy tissues and doses to individuals in close communication, M. Pollycove, November 1993).
proximity to the patient. The more significant The resulting estimate is about 50,000 treatments therapeutic appucations are described below. per year.
in the past, therapeutic quantities of iodine-131 Ilyperthpo;dism for treatment of hyperthyroidism tended to be of Ilyperthyroidism is characteri7ed by an increased a magnitude (185 to 550 megabecquerels production of thyroid hormone. Ilyperthyroidism (5 to 15 millicuries)) that would reduce the 6
]
i hormone production of the hyperactive tnyroid Estimates of the frequency of radioactive iodine !
gland to normal levels. However, experience treatment for this condition are included under demonstrated that over a period of years the the estimates for hyperthyroid treatment above. ,
j therapeutically induced cuthyroidal condition '
(normal or healthy thyroid) deteriorated to one of 'llyroid Cancer hypothyroidism requiring thyroid hormone There is no nationwide cancer registry that ,
replacement therapy. As a result, today i hyperthyroid therapy also involves the use of accurately defines the number of new cases of iodine-131 to ablate the thyroid. Approximately cancer diagnosed each year. However, the -
50 percent of all hyperthyroid patients undergo American Cancer Society (ACS) annually . - .
ablation (personal communication, M. Pollycove, publishes data on cancer incidence and patient January 1996). Typically, activities in the range survival based on information provided by the from 550 to 1,110 megabecquerels (15 to National Cancer Institute's Surveillance, 30 millicuries) are used but about 2 percent of all Epidemiology, and End Results (SEER) program.
patients require as much as 2,220 megabecquerels (60 millicuries), the maximum typically The ACS estimates of United States cancer cases administered. Such doses quickly result in the diagnosed for 1992, are based on age-specific totalloss of thyroid function and the patient is incidence rates from the SEER program for 1986 given hormone replacement therapy from the to 1988 applied to the Census Bureau's population onset (personal communications, F. A. Mettler, projections for 1992. The ACS's estimate of new ,
March 1993 and M. Pollycove, January 1996). thyroid cancers in 1992, is 12,500 (ACS93). This l i
report assumes that 100 percent of these cases Thyrold Nodules will be treated by the surgical removal of thyroid gland tissue (i.e., thyroidectomy). Following Single or multiple nodules of sufficient size may surgery, about 20 percent of these cases will not cause obvious enlargement of the thyroid. A require additional thyroid cancer therapy but nodule (s) refers to a replacement of the normal about 80 percent will require additional j
homogeneous cytostructure of the thyroid with a therapeutic administrations of iodine-131 to histologic pattern ranging from colloid-filled cysts eliminate residual thyroid cancer tissue (personal l and colloid adenomas to follicular adenomas. communication, M. Pollycove, January 1996). l Since the incidence is 4 to 5 times as great in Therefore, this report assumes that about women as in men, and since it develops and 10,000 cases per year will be treated with progressively increases in size during life, it is therapeutic doses of iodine-131.
nost freques ly found in females 50 to 70 years of age. It is not uncommon for nodules to remain The quantities of iodine-131 used in thyroid undetected until a post mortem examination. cancer therapy depend upon the type of cancer, the status of the cancer, and the degree of uptake Small nodules in cuthyroid subjects require no and retention of iodine-131 by residual cancerous therapy. If the gland is grossly enlarged and thyroid tissue. As a result, current therapeutic causes a cosmetic problem or tract.eal quantities range from 1,850 to compression, treatment may be indicated along 11,100 megabecquerels (50 to 300 millicuries) with thyroid hormone replacement therapy. (personal communications, F.A. Mettler and K.L.
Miller, March 1993). The typical quantity A small percentage of thyroid nodules tend to administered is 5,500 megabecquerels produce thyroid hormones uncontrollably c id in (150 millicuries) (personal communication, M.
excess (i.e., the nodule is not u'nder the regulatory Pollycove, January 1996).
control of the pituitary gland and is clinically referred to as toxic nodular goiter). The presence 'Iherapy for Polyc3themia Vera of these autonomously functioning thyroid nodules Since the introduction of radiophosphorus in 1936, leads to hyperthyroidism (i.e., thyrotoxicosis).
patients with polycythemia vera have been treated Toxic nodular goiter, like Graves' Disease, may be successfully with this radioisotope to control rather than cure this disease. Polycythemia vera treated surgically (i.e., thyroidectomy) or by therapeutic dose (s) with radioactive iodine, is a relatively rare disease that is characterized by 7 NUR EG-1492
'O s.
an autonomous proliferation of marrow cells Intra-Arterial Herapy leading to an over production of red blood cells, white blood cells, and platelets. Typically, Some primary tumors as well as metastatic lesions phosphorous-32 (P-32) is administered are highly vascularized. Direct arterial injection intravenously in doses of 111 to 185 megabec crels with insoluble radiolabelled particulates that lodge (3 to 5 millicuries) per treatment over a period of in arterioles and capillaries of the tumor is the time with average cumulative quantities of basis of this form of therapy (EH87, Zl84).
740 megabecquerels (20 millicuries) per patient. Insoluble carriers of radionuclides that have been clinically tested include iodine-131-labelled oil contrast medium, iodine-131 lipoidal or -ethiodol Hone Herapy (PA87), yttrium-90-glass microspheres (HE88),
and yttrium-90 (Y-90) resin particles (ROE 90).
Since the use of radioactive strontium for the Since these therapies are so seldom used, their treatment of bone metastases was first described impact may be ignored in this analysis.
in early 1942 (PE42), bone therapy has included other radionuclides. Bone therapy may involve Intracavitary Tumor Herapy the treatment of primary bone tumors such as osteosarcoma (BIE7) in which bone-seeking For tumors that are spread over the serosal radiopharmaceuticals are in fact tumor seeking. linings of the body cavities or for ascites tumors, Bone therapy may also be the treatment of painful one approach to delivering therapeutic doses of skeletal metastases, which may be palliated by radiation is to inject the radiopharmaceutical bone-seeking radionuclides. Although the directly into the body cavity. For tids approach, literature references the palliative and tumor colloids, chelates, and, more recently, monoclonal therapeutic use of these radionuclides antibodies labelled with gold-198 (Au-198),
i (phosphorous-32: CH80, RO77; strontium-89 phosphorous-32, yttrium-90, or iodine-131 can be (Sr-89): BL88, KL87, RO87, ROE 90, S185; used.
rhenium-186 (Re-186): KE87, MA88, SC90; samarium-153 (Sm-153): LA90, TU89), there are laitially, gold-198 colloids were used, but no databases and no studies have been performed phosphorous-32 is now preferred due to its longer that would allow quantitative estimates regarding half-life, more energetic beta particles, and the the number of patients given bone therapy with absence of gamma radiation. Intracasitary radiopharmaceuticals. These other therapies are radionuclide therapy with phosphorous-32 in performed so seldom that they have negligible quantities of 185 to 370 megabecquerels (5 to impact in ecmparison with the radiolodin" 10 millic"M has been appliad to malignancies invohing the pleural, pericardial, and peritoneal Herapy with Radiolabelled Cells
' *OA ' ' }'
More recently, iodine-131- or yttrium-90-tabelled For lymphoid cell malignancies, the tumor cells tumor-associated monoclonal antibodies have (i.e., lymphocytes) may retain their ability to been used in intracavitary therapy (F189, PE86, migrate and recirculate into the lymphoreticular R190) in doses of 740 to 2,220 megabecquerels tissues (i.e., spleen, liver, bone marrow, and lymph (20 to 60 millicuries). Superiority of monoclonal 4 nodes). The harvesting, labelling, and reinjection antibodies over colloids is expected due to the of lymphocytes has been demonstrated to deliver enhanced affimity of the labelled antibody for the therapeutic levels of radiation doses to tumors of target cells. At present, these therapies are rarely the lymphoreticular system (CO87). Indium-114- used and thus have no impact in comparison with lab'elled lymphocytes have a potential therapeutic radiciodines.
role in the management of lymphoma, and clinical studies are underway. Because use of this new Radioimmunotherapy therapy is not widespread, its impact may be omitted in this analysis, but it should be noted Radioimmunotherapy involves the use of that use of a dose-based methodology provides a radiolabelled antibodies directed against means to determine the quantities for which tumor-specific antigens such as the release may be authori7ed. carcinoembryonic antigen (CEA) and ferritin.
Only a very limited number of cancer patients tumor cells within a short distance of the implant.
have been treated experimentally with The major advantage of brachytherapy over radiolabelled antibodies in combination with external irradiation in the treatment of solid chemotherapy and external beam irradiation. tumors is the favorable ratio of dose delivered to Among cancers treated are hepatomas, Hodgkin's tumor cells versus normal tissue. This is disease, and non-Hodgkin's lymphoma (LE85, plicularly true of prostate cancer where the NE90, OR85). In the past, radioimmunotherapy surrounding normal tissue includes the bladder, involved the use of iodine-131. and yttrium rectum, and urethra. The presence of these labelled polyclonal antibodies raised against normal tissues limits the dose of external beam ~~
tumor-associated antigens in a variety of animal . radiation therapy that can be administer'e'd' safely species. Based on avidity of tumor cells and to the prostate.
exposure considerations of the bone marrow, single doses of 370 to 1,110 megabecquerels ~'he radionuclides primarily used in permanent (10 to 30 millicuries) have been used. implants are iodine-125 and palladium-103. less frequently used radionuclides include gold-198 and The development of the hybridoma technique by ytterbium-169 (Yb-169).
Kohler and Milstein (KO75) has caused significant shift in radioimmunott.crapy. The hybridoma The most frequently used radionuclide in technique allows the development of monoclonal permanent implants is iodine-125, which has the antibodies against tumor-associated antigens. At advantage of an extremely low energy (27 kev) this time, however, the use of radiolabelled photon and a physical half-life of 60 days. Besides monoclonal antibodies fo- therapeutic applications minimizing dose to surrounding healthy tissue, the has been limited to experimental treatments. At low photon energy also limits doses to hospital present, these therapies are rarely used and thus personnel and others when compared to have no impact in comparison with the temporary implants with iridium-192 or radiciodines. permanent implants with gold-198 (CL89, RU92).
Although iodine-125 implants are most commonly 4.1.2.2 Radioactive Materials Used in Permanent used to treat cancer of the prostate (DE86, FU91, implants (Brachytherapy) HE82, MO88, PR92, WH88), they have also been used on a very limited basis for brain tumors In-situ radiotherapy may involve permanent (AG92, OS92, SC92), carcinomas of the pancreas implants or brachytherapy. Brachytherapy has (MO92), non-oat cell lung carcinomas (FL92),
been around almost since the discovery of X raya. brwt cancers (RU92), and tumors of the head, Brachytherapy can be divided into temporarv neck, and eye.
implantation using high activity sources or permanent brachytherapy using the interstitial Palladium-103 seeds were developed for use in implantation of encapsulated radioactivity. In brachytherapy to reduce some of the problems 1911, Pasteau reported the first treatment of associated with iodine-125. Its average photon prostate cancer by brachytherapy using radium energy of 21 kev is Lower than iodine-125, but, inserted through a urethral catheter (Pall). given its shorter 17 day half-life, it has a higher Currently, iridium-192 (Ir-192) is the radionuclide initial dose rate. Recently, palladium-103 seeds of choice for temporary implantation. For have been developed with the same physical temporary implantation, the sources are removed parameters as iodine-125 seeds to ensure from the patient before the patient is released compatibility with the brachytherapy tubes and from licensee control. Radionuclides used for templates used for iodine implantation (ME90),
temporary implants are, therefore, of no concern to this report and will not be discussed further. Ytterbium-169 has been hailed as a repixement for iodine-125 in brachytherapy. Compared to Over the past 20 years, several radionuclides have iodine-125 and palladium-103, it has a slightly been introduced to brachytheiapy, allowing for the higher initial dose rate, and its average 93 kev permanent implantation of radioactive " seeds." beta energy allows for a more favorable dose Seeds are miniature capsules that are strategically distribution and negligible tissue self-attenuation inserted within a solid tumor and over the period (Poo0). However,its use as a permanent implant of their decay deliver a lethal dose of radiation to is nominal due to the presence of a small(less 9 NUREG-1492 l
I
than 3 percent) average photon peak at 300 kev, annually, at activities ranging from 2,775 to that can significantly impact radiation doses to 4,625 megabecquerels (75 to 125 millicuries),
individuals in proximity to the patient.
4.1.2.3 Summary of nerapectic Gold-198 implants have been used in a few Administrations instances of prostate cancer (CA88, FR88). The potential advantage of delivering a high dose Table 4.4 summarizes the range of the activities of within a relatively short time, however, is offset by gamma-emitting radionuclides used in therapeutic its energetic gamma emissions, which has caused administrations and the estimate.s of da amabers its use in recent years to fall into disfavor and be of each therapy performed annually.
used only rarely (CA87).
A thorough search of the literature and personal 4.2 Assessment of Doses to communications with several prominent members Individuals Exposed to of the medical and scientific community (see patients Administered Acknowledgements) indicates that there is no Rad.ioact.ive Mater.ials published data available to quantify the annual number of cancer patients receiving permanent implants. However, the scientific literature and To identify the potential impacts associated with consensus opinion among the experts identified m . each of the alternatives, it is necessary to know the acknowledgments to this report does support the magnitude of doses that could be received by tile foHowing: an individual exposed to a patient who has been administered radioactive materials. While
- 1. permanent implants are currently considered y;, g g g. ;
an appropriate treatment for only a few sites pathways by which radionuclides are removed of solid tumors; from the body (e.g., exhalation, feces, saliva, !
sweat, urine, and possibly vomit), experience
- 2. among the cancer sites for which permanent mdicates that for iodine.131 and other gamma implants are currently employed, prostate emitters, these pathways will generally be J cancer represents the overwhelm,mg major.ty; i tasignificant in relation to the doses that can
'**" .fr m exposure to the direct gamma
- 3. among the 13;000 annual new cases of radiation from the patient, with the exception of prostate cancer (ACS93), only a small intake from the milk in breast feeding infants.
f ction is treated vith permanent implants; This section of the report assesses the external and, and internal doses to individuals, including a breast-feeding infant, exposed to patients who 4 for the purposes c,i th.is w alys.ts, implants have been administered radioactive materials.
mvolving gold-198 (largelo discontinued) and
- ytterbium-169 (isolated vse only) may be 4.2.1 Methodology for Calculating e ignored.
' External Gamma Dose In the absence of documented clinical data, The methodology for calculating the external information was sought from the implant vendors on numbers of administrations and typical gamma dose from exposure to the released activities of radioactive material used per patient is also described in the associated administration. Currently, there are only three regulatory guide for the final rule (NRC97). The j
vendor sources. Vendor supplied data suggests methodology is based on the one employed in the that approximately 2,000 implants involving National Council on Radiation Protection and iodine-125 are performed annually, at activities Measurements (NCRP) Report No. 37, l
- ~ *Precautionsin the Management of Patients Who ranging from i 110 to 1,850 megabecquerels 4 (30 to 50 millicuries). For palladium-103, llave Received Therapeutic Amounts of '
approximately 1,500 impiants are performed Radionuclides" (NCRP70).
NUlmG-1492 10 i
i O
l 1
l l
l Table 4.4 Number of Annual Therapeutic Administrations in the United States (significant !
l gamma-emitting radionuclides only) l Range of Activities Estimated No. of "Iherapeutic Radionuclide Administered Administrations Employed (MBq) (mCl) (per year)
Procedure 370 - 2,220m (10 - 60) 50,000 Thyroid Ablation and 1-131 l{yperthyroidism . , , _ ,
Thyroid Cancer I-131 1,?50 lt!F" . (50 - 300) 10,000 l l
1,110 - 1,850m (30 50) 2,000 Permanent Implant I-125 ,
2,775 - 4,6255 (75 - 125) 1,500 Permanent Implant Pd-103 63,500 Total
- Based on personal communications, F. A. Mettler March 1993 and M. Pollycove, January 1996.
- Based on personal communications. F. A. Meuler sad K.L. Miller, March 1993.
- Based on information supplied by implant vendors, August 1993.
To calculate the dose to total decay D(co), the when most of the dose is dHivered in a relatively regulatory guide uses the following equations. short time.
For radionuclides with a half-life greater than 1 day Doses among individuals who may come in e P(.5) contact with a released patient are highly variable D(a) = (1) '
and reflect the crucial, but difficult to define, (100 cm)2 parameters of time, distance, and shielding.
Based on time and distance considerations,it is reasonable to conclude that for the overwhelming and for radionuclides with a half-life less than or equal to 1 day majority of released patients, the maximally exposed individual is likely to be the primary care-34.6PQ,Tr prodder, a family member, or any other individual p(,,) , (2) who spends significant time close to the patient.
(100 cm)2 ,
Based on time, distance, and shielding factors, which describe normallifestyles of the United where P = exposure rate constant for a point source, R/ mci-b at 1 cm, States population, it is highly unlikely that doses equal to spending 100 percent of time at a distance of 1 meter from a patient would result to Q, = initial activity of the point source in millicuries, at the time of release, any individual including a patient's spouse. As a standard medical practice, patients undergoing therapeutic treatments with radiopharmaceuticals T, = physical half-life in days, are given firm instructions, both verbally and in 4 2.1.1 Occupancy Factor writing, regarding basic principles on how to minimize doses to other individuals.
Equation 1 assumes, for radionuclides with Given all considerations, a reasonable estimate of half-lives greater than i day, that the individual the maximal likely dose to an individual exposed likely to receive the highest dose from exposure to to a patient is 25 percent of the dose to total the patient would receive a dose of 25 percent of the dose to total decay (0.25 in Equation 1) at a decay at a distance of 1 meter (except for the distance of 100 centimeters (1 meter). For short-lived radionuclides). The selection of an radionuclides with half-lives no greater than 1 day, occupancy factor of 25 percent at I meter for the factor 1.0 is used in Equation 2 because the estimating maximal likely exposure is based on the authors' professional judgment of time-distance assumption that the time that individuals will combinations that are believed likely to occur spend near the patient will be limited is not valid 11 NUREG-1492
Table 4.5 Family Doses from Patients Tmted with lodine-131 for Thyroid Carcinoma Measured Predicted Total Body Hurden Doses to Dose Based on Activity at Time of Family Occupancy Factor of Administered Dischaq;e Members 25% at 1 meter Patient (mCl) (MCI) (mrem) (mrem) 1 210 25.2 --ov,70,30 386 50,20,20 404 2 311 " ~ 26.4 209 18.4 80,40 282 3
Source: !!A74.
when instructions to minimize time spent close to demonstrates that if reasonable efforts to maintain distance are not made doses can be higher than the patient are given.
predicted by Equation 1.
The occupancy factor of 0.25 at 1 meter is also Buchan and Brindle (BU71) monitored the doses j supported by empirical data. Harbert and Wells (HA'!4) monitored the external dose of 8 family of 54 family members of patients who underwent I members of 3 patients treated for thyroid iodine therapy for hyperthyroidism. This study is carcinoma using iodine-131. All doses to family interesting because no instructions on minimizing members were far below 5 millisleverts (0.5 rem) dose were given. Thus, the results can be taken as shown in Table 4.5. The last column of to represent the doses that would be received if Table 4.5 provides dose estimates based on the no instructions were given or if instructions were l totally disregarded. The highest measured dose to I occupancy factor of 25 percent at 1 meter in Equation 1. The actual doses are far below the a family member was 2.7 millisieverts (0.27 rem), l calculated doses for an occupancy factor of much below the 5-millisievert (0.5-rem) limit.
25 percent at 1 meter, indicating that the model The effective occupancy factor at I meter was less generally provides a conservative estimate of the than or equal to 0.25 in 45 of the 54 cases (83 dose, percent). Thus, even in the complete absence of instructions, the occupancy factor at 1 meter was usually less than 0.25. i Harbert and Wells (HA74) also measured the !
external doses to 11 family members of seven in conclusion, both empirical measurements and l hyperthyroid patients. All doses to family l members were far below 5 millisieverts (0.5 rem). professional judgement support an occupancy in each case, the measured doses were at least a factor of 0.25 at 1 meter as a generally factor of 10 below the doses predicted by Equation 1 conservative value. Using this value in Equation 1 using an occupancy factor of 0.25 at 1 meter. should generally overpredict the dose even if instructions are not given or are not strictly followed. However, higher occupancy factors are Jacobson et al. (JA78) measured the external doses to 10 family members of 7 iodine therapy certainly possible in situations where instructions patients. In each case except one, the external are disregarded and are not considered a problem dose to the family member was below that for this rulemaking. The NRC's rulemaking based on Alternative 3 provides an adequate level predicted by Equation 1 using an occupancy factor of 0.25 at 1 meter and well below 5 millisieverts of protection with a significant margin of safety (0.5 rem). In the case of the exception, the family for those families that make a reasonable effort to went on an extended vacation spending much of follow the instructions. The NRC considers that the time together in an automobile. This to be sufficient.
12 N U Rl!G.1492
4.2.1.2 Exposure Rate Constant both of which are dependent upon the physical condition of the patient. Table 4.6 provides the The exposure rate constant P expresses the dose uptake fraction and biological half-life for each rate per hour at 1 centimeter in air for a component with respect to patients being treated 37-megabecquerel (1-millicurie) point source of for hyperthyroidism (and thyroid ablation) and a given radionuclide. The exposure rate constants thyroid cancer. The extrathyroidal and thyroidal and the physical half-lives of radionuclides used in uptake fractions for thyroid cancer assume medicine are shown in Table A.1 of Appendix A. surgical removal of the thyroid gland prior to
~- - - - -
iodine-131 therapy.
For permanent implants, a significant reduction in the dose and dose rate occurs from the shielding To determine the total dose to an individual ;
effects of the source capsule. For iodine-125 and exposed to a patient administered iodine-131, palladium 103 implants, the dose to total decay at considering biological retention and elimination by 1 meter was calculated using an exposure rate the patient, Equation 1 must be split into two constant corrected for capsule shielding as shown terms that separately represent the dose in Table A.1 of Appendix A. The physical contribution from the thyroidal and extrathyroidal characteristics of other radionuclides used in components. The following equation was used to permanent implants (e.g., gold 198 and calculate the total dose to complete decay ytterbium-169) are also given in Appendix A. assuming an occupancy factor of 0.25 at 1 meter:
4.2.1.3 Biological Retention and Elimination 34.6PQ,Tg F (0.25) g g, 3 ElTective Half-Life (100 cm)
A licensee may replace T in Equations (1) and 34.6PO,T2c F 2(0.25)
(2) with the effective half $ life T,of the ,
radioactive material to demonstrate compliance (100 cm)2 with the dose limit in the revised 10 CFR 35.75.
T,is characterized by 7, and the biological half-life T, of the radionuclide (which accounts for where Tg = effective half-life of the extrathyroidal the biological retention and elimination of the component in days (based on the radionuclide from the patient's body) according to . biological half-life T, of the the equation thyroidal component),
I =t extratnyroidal uptake fraction, T, = '
T'. (3)
T, + Ts T,2 = effective half-life of the thyroidal component in days (based on the on the biological half-life T,2 of the Under the final rule a licensee could authorize release on a case-by-case basis based on the thyroidal component),
biological half-life rather than only the physical half-life of the radiopharmaceutical. F = thyroidal uptake fraction, liiological Retention and Elimination of lodine 131 P = exposure rate constant for a point source, R/ mci.h at I cm, For iodine-131, biological retention and elimination are characterized by the fractional G, = initial activity of the radionuclide in amounts that reside in the thyroid (i.e., thyroidal millicuries, at the time of release.
component) and in the rest of the body (i.e.,
extrathyroidal component). Each component has This equation is only val;d if the release occurs at a specific fractional uptake and biological half-life, the time of administration.
1 13 NURiiG 1492
Table 4.6 Iodine-131 Biological Retention and Elimination Parameters for Ilyperthyroidism, Thyroid Ablation, and 'Unyroid Cancer
- Extrathyroidal Thyroidal Component Component Uptake Biological Uptake Biological Fraction llalf Life Fraction llalf-Life Disease ?; - - Tu (days) F Tu (days)
~
0.10 033 0.90 10 Hyperthyroidism and 0.20 033 0.80 15 Thyroid Ablation 030 033 0.70 20 0.40 033 0.60 20 0.50 033 0.50 25 033 0.40 40 0.60 0.70 033 030 65 033 0.05 80 Thyroid Cancer 0.95
- Data taken from ICRP Publications 30 GCRP78),53 GCRP87), and 56 GCRP89), and personal communication, M. Pollycove, March 1996, based on his clinical experience.
l l
i 4.2.1.4 'Dssue Shielding for Permanent implants the lungs, brain, pancreas, etc., tissue shielding values of similar magnitude can be assumed for !
an adult male and female. liowever, for certain In addition to the shielding effects of the source implants involving primary cancers of the neck capsule (see 4.2.1.2 Exposure Rate Constant), a and head, overlying tissues may provide less than significant reduction in the dose and dose rate also occurs from the tissue surrounding the 5 HVLs of attenuation. In such instances,it is standard practice to provide the patient with a implant. For a prostate implant, tissues that serve small portable shield" which effectively attenuates to reduce photon flux about the patient include the soft and bone tissues of the thighs, pelvis, ell emissions (personal communications, C. Jacobs, buttocks, abdomen, etc. The linear *"~ "-don August 1993, and R. Nath, J. St. Germain and coefficient and corresponding soft tissue half-value K. Suphanpharian, March 1993). A shield consists layer for the 27 kev photon of iodine-125 are of inyl sheet impregnated with lead and molded to fh the anatomical surface over the implant l 0387 cm 4 and 1.8 cm, and for the 21 kev photon of palladium-103,0.770 cm4 and 0.9 cm, j For the purposes of this analysis, irnplants will be respectively (JOli83). j evaluated considering shielding by tissue '
To assess the impact of tissue shielding by the equivalent to 5 half value layers.
patient, the medical physicist of the Memorial Sloan Kettering Cancer Center was consulted 4.2.2 Assesstnent of Internal Exposure (personal communication, J. St. Germain, March 1993). Based on empirical assessment invoh'ing 4.2.2.1 Internal Exposure Pathways patients with prostate implants, tissue shielding for j
iodine-125 is likely to exceed 5 or more half-value Upon oral administration or direct injection into layers (IIVLs), which would reduce the dose and the circulating blood, the radiopharmaceutical dose rate by a factor of at least 32. For undergoes the normal processes of absorption, distribution, and excretion. Removal of palladium-103 implants, in which the IIVL in tissue is less than I centimeter, the shielding radionuclides from the patient's body may follow afforded by the patient's tissue is even more the pathways of breast milk, exhaled air, feces, extensive. For other implants invohing saliva, sweat, urine and vomitus.
14 N L : R EG.1492
l I
I Ilreast Milk. Radionuclide excretion via the 4.2.2.2 Measurements of Internal Exposure mammary gland constitutes a potential exposure pathway to the breast-fed infant. This can be a The potential for contamination by patients ,
very important pathway after the administration of treated with radiciodine which may serve as a radioiodines. Relatively small administrations of source for internal exposures to others have been radiciodine to a breast-feeding women can cause assessed for various excreta pathways (BL71, l very large doses to the thyroid of the infant. MA73, NI80). Maximum excretion rates are Cessation of breast-feeding for iodine observed shortly after an administered dose.
administrations avoids the potential for thyroid Excretion rates decline rapidly thereafter due to ablation in the infant. renal clearance and thyroidal uptake. Almost all the excreted activity is excreted in the urine.
Exhaled Alr. Exhalation is the principal patimay Contamination through urinary excretion may be for the elimination of radioactive gases sucl. f. readily controlled by cautious but reasonable xenon-133, which is used for lung ventilation tests. hygiene pra3 ices.
Through passive diffusion, unbound iodide in the circulating blood may also be exhaled. In a thorough study of two patients treated for thyroid carcinomas, Nishizawa, et al. (NI80)
Feces. Radiopharmaceuticals retained or observed maximum excretion rates of iodine in catabolized by the liver may be secreted into exhalation, perspiration, and saliva of the gastrointestinal lumen via the bile. Biliary 3.2 x 104/hr,2.4 x 104 /hr, and 6.3 x 104/hr of the secretion of a radionuclide may be followed by administered dose, respectively. Thus, the intestinal reabsorption. amounts in exhalation and perspiration were very small. The amount in saliva is larger, but transfer Saliva. Salivary excretion of radionuclides is also of saliva to other people is likely to be limited.
proportional to the unbound or diffusible fraction in the plasma. However, salivary excretion is A British study (BU70) estimated thyroid seldom an important climination route, since radioiodine activity in 39 subjects who, as family nearly all saliva is swallowed rather than members, were associated with patients treated expectorated. for hyperthyroidism. Administered quantities ranged from 148 to 740 ruegabecquerels (4 to Sweat. Radionuclides present in the :xtracellular 20 millicuries) per patient. Of the 39 patients,28 fluid will tend to be excreted in the sweat in were instructed to take precautionary measures to accordance with the fraction that is unbound in minimize exposure to family members. Eleven the plasma, patients volunteered to disregard special precautions against contamination and minimizing Urine. Radionuclide excretion in the urine is the spousal and family exposure. On the basis of one dominant and almost universal elimination measurement per family, subject thyroid burdens pathway. ranged from less than 37 to 1,110 becquerels (1 to )
30 nanocuries) with an average of 259 becquerels Vomitus. The occurrence of vomiting is not (7 nanocuries). Thus, the uptake of radioiodine related to the administration ofiodinc.131 or any by family members was only about 1 millionth of other radiopharmaceutical (personal the administered quantity, and the dose from the communication, M. Pollycove, August 1995). uptake was less than 0.01 millisievert (1 millirem)
Furthermore, vomiting is seldom an important committed effective dose equivalent. This internal ,
dose is negligible compared to the external dose. l elimination route, since orally administered radiopharmaceuticals such as iodine-131 are The authors concluded that contamination is not rapidly absorbed, within a half hour, by the important and "except where young children are gastrointestinal system. Ilowever, a significant involved, precautions to minimize contamination portion of the administered radionuclide could be should be abandoned."
excreted if vomiting occurs immediately fo!!owing the administration, in this case the patient in a 1978 study by Jacobson, et al. (JA78), seven families were studied in which one family member typically would not have been released, and the licensec would be able to limit exposure and clean nad been treated with iodine 131 doses ranging up contamination. from 2% to 5.500 megabecquerels (8 to d NUREG-1N2 l
150 millicuries). Non-patient family members Table 4.7 indicates that, except for some were assessed for external exposures by means of procedures using iodine-131 to detect thyroid thermoluminescent dosimeters (TLDs) worn at cancer, none of the other diagnostic procedures the wrist for the full duration of exposure. currently being performed have the potential to Internal exposure (i.e., thyroid burden) v- deliver a 1 millisi: vert (0.1 rem) dose to an determined at discrete time intervals by means of individual ewsed to a patient. However,in the a pair of 30-inch Nal crystals. Although all family case of iodin 131, the effective half-life of the m, embers proximal to the patient had measurable extrathroidal omponent is much shorter than the thyroid burdo <fose estimates in nearly all cases physical-life used to calculate doses. Therefore, indicate tha. internal committed effective dose the dose would be much lower than Se c :. -
equivalents were always less than 10 percent of shown in Table 4.7. Since the doses in all cases the 5-millisievert (0.5-rem) dose limit, even when are much below 1 millisievert (0.1 rem),
no precautions were taken, and the external dose diagnostic procedures will not be considered any substantially exceeded the internal dose. further in this analysis.
The investigators also concluded that it " . . . 4.2.3.2 nerapeutic Procedures appears certain from our study of these subjects that for spouses, there is a relation between The results of the dose calculations for thyroid activity and intimacy. Of the 12 husbands therapeutic procedures using the physical and and wives questioned, . . . none were willing to effective half-lives (as applicable) are summarized adjust living habits with their spouses because of in Table 4.8. All calculations assume an the radiation therapy. Most, however, are concerned occupancy factor of 25 percent at a distance of for their children and are willing to listen to 1 meter and immediate release of the patient by suggestions which minimize exposure to their the licensee (i.e., no hospitalization). For children." While the authors are vague about hyperthyroidism (and thyroid ablation), doses what they mean by " adjust living habits," it appears based on effective half-life have been calculated that couples are often u villing to abstain from using the four thyroidal uptake fractions that brief periods of close intimate contact for prolonged characterize the majority of patients with this periods of time. This should not be a problem disease. Table 4.8 indicates that the model because the brief times will be too short to add considering biological retention and climination significant external dose and transfer of contamination provides dose estimates that are significantly less is not a significant contributor to internal dose. than the model thr.t considers physical half-life only.
Thus, the stadies on internal exposures s%._.
that internal doses from intake of contamination For the purposes of this analysis, the dose are likely to be much smaller than doses from estimates for iodine-131 based on the biological external radiation and much smaller than the model will be used because this model more public dose limit. Therefore, internal exposures closely reflects the behavior of iodine-131 in will not be considered in this analysis other than humans. For permanent implants, biological for the breast. feeding infant. modeling does not apply. In this case, this analysis uses the dose estimates based on the physical half-life. Only the therapies involving 4.2.3 Estimate of Maximum Likely radioiodme would be affected by any of the Doses to Individuals Exposed to alternatives under consideration.
Patients .
4.2.4 Assessment of Doses to Breast-Assessments were made of the doses that could Feeding Infants result from exposure to a patient treated vith each of the radionuclides und. If a radiopharmaceuticalis administered to a woman who is breast-feeding an infant, a fraction 4.2.3.1 Diagnostic Procedures of the quantity administered may be deposited in j the breast milk and may be transferred to the The results of the dose calculations for dignostic infant. In considering the dose to the individual I procedures are summarized in Table 4.7. likely to receive the highest dose from exposure to N Ult EG.1492 16
a Table 4.7 Maximum Likely Doses to Total Decay to Exposed Individuals from Diagnostic Procedures Activity per ,
Examination Type ,
Examinationm Gamma Dosem (Radiopharmaceutical) (MBq) (mCl) (mSv) (rem)
Brain 740 0.13 (0.013)
- Tc-99m DTPA (20) 740 (20) 0.13 (0.013)
- Tc-99m O.
Hepatobiliary 18.' 0.03 (0.003)
- Tc-99m IDA (5)
Liver 185 (5) 0.03 (0.003)
- Tc-99m Sulfur Colloid Bone
- Tc-99m Phosphate 740 (20) 0.13 (0.013)
Lune Perfusion 185 0.03 (0.003)
- Tc-99m MAA (5)
Thyroid 185 (5) 0.03 (0.003)
- Tc-99m O.
3.7 (0.1) 0.02 (0.002) 131 370 (10) 1.5 (0.15)
- I-131 (maximum)
Cardiovascular 740 (20) 0.13 (0 013)
- Tc-99m RBC
- Tc-99m Phosphate 740 (20) 0.13 (0.013) 111 (3) 0.04 (0.004)
- TI-201 Chloride Renal
- Tc-99m DTPA 740 (20) 0.13 (0.013) 9.3 0.04 (0.004)
- I-131 Hippuran (0.25)
"' De activity la the typical quantity administered per examination (see Table 4.2). ne maximum diagnostic activity of I-131 is shown because it yields gamma doses exceeding 1 millisievert (0.1 rem).
- Calculations assuine no biological elimination, no attenuation of gamma rays in air or body of patient, and occupancy factors of 100 percent at a distance of 1 meter for Tc-99m and 25 percent at a distance of 1 meter for 1131 and TI-201.
17 NUREG.1492
1 e
I l
Table 4.8 Maximum Likely Doses to Total Decay to Exposed Individuals from Therapeutic Procedures '
Assuming No llospitalization
, Gamma Dose Based on EITective flatf Life
- Gamma Dose Extrathyroidal Thyroidal l Based on Component Component l Therapeutic Activity Physical Uptake Uptake llatf-Lifem Fraction Fraction Dose Procedure Administered (Radionuclide) (MBq) (mCl) (mSv) (rem) F, F2 (mSv) (rem) livnerthyroidism A Thyroid Ablation"
- iodine-131 370 (10) 1.5 (0.15) 0.40 0.60 0.67 (0.067) 0.50 0.50 0.61 (0.061) 0.60 0.40 0.58 (0.058) !
0.70 030 0.45 (0.045) l l
1,110* (30) 4.6 (0.46) 0.40 0.60 2.01 (0.201) 0.50 0.50 1.83 (0.183) 0.60 0.40 1.74 (0.174) 0.70 030 135 (0.135) 2,220 (60) 9.2 (0.92) 0.40 0.60 4.02 (0.402) 0.50 0.50 3.66 (0366) l 0.60 0.40 3.48 (0348)
O.70 030 2.70 (0.270)
Thyroid Cancer
- iodine-131 1,850 (50) 7.6 (0.76) 0.95 0.05 0.62 (0.062) 5,5505(150) 22.9 (2.29) 0.95 0.05 1.86 (0.186) 7,400 (200) 30.6 (3.06) 0.95 0.05 2.48 (0.248) ,
Permanent Implant" 1,110 (30) Effective 11alf-Life Not Applicable to ;
- iodine-125 0.54 (0.054) 1,480* (40) Permanent Implants l 0.72 (0.072) '
1,850 (50) 0.90 (0.090)
- palladium-103 2,775 (75) 0.29 (0.029) 3,7005 (100) l 039 (0.039) 4,625 (125) 0.49 (0.049)
"' Maximum likely dose based on an occupancy factor of 25 percent at a distance of I meter. l
- Doses have been calculated for the four thyroidal uptake fractions that characterize the majonty of patients treated.
"' Typical activity administered.
- These dose values account for the 5 HVL.s of tissue shielding by the patient and. therefore. are equal to the point source dose in air divided by 32.
18 N UllEG-1492
l l
l 1 millisievert (0.1 rem). If the sum of the doses a patier.1 who has been administered a in Columns 3 and 4 of Table B.5 (i.e, internal radiopharmaceutical,it is necessary to consider '
(maximum value) and external doses, respectively) both the internal and external dose to the infant for a radiopharmaceutical exceeds I millisievert from breast-feeding. (0.1 rem), then instructions would be required l
4.2.4.1 Internal Dose 4.2.4.3 Special Considerations for Iodine-131 Sodium lodide !
The potentialinternal dose to the breast-feeding l infant was calculated for the maximum normally There are specific issues associated with the '
administered quantities of con..nonly ted administration of iodine-131 sodium iodide in tha diagnostic and therapeutic radiopharmaceuticals. following botn diagnostic and therapeutic The results of the calculations are shown in administrations, the dose to a breast-feeding child Appendix B. could exceed 5 millisieverts (0.5 rem) if there was no interruption of breast-feeding. In particular,if The doses can be represented as a range where the woman does not cease breast-feeding after the range covers the minimum and the maximum administration of millicurie quantities of transfer of radioactive material from published iodine-131 sodium iodide, the internal dose to the >
data. The range is due to individual variability breast-feeding infant could be large enough to and measurement variability as indicated by cause the infant's thyroid to be seserely damaged, concentrations measured in breast milk. Doses resultingin hypothyroidism. If hypothyroidism
~
were calculated for newborn and one-year-old were tir2 '.iagnosed in very young c 1dren, severe infants. Since the doses for newborn infants are mental retardation may occur. However,if the higher, those doses were used in the analysis. patient was provided instructions to discontinue '
The internal dose ranges for commonly used breast-feeding, as well as being advised of the radiopharmaceuticals assuming no interruption consequences of of not following the instructions, the breast-feeding are shown in Column 3 of NRC believes that the probability of a woman Table B.5 (see Appendix B). The radionuclides in failing to cease breast-feeding after being the table that are not regulated by the NRC administered iodine-131 sodium iodide is smal (e.g., Ga-67) are omitted from further For example,in 1990 an administered dosage of consideration in this analysis. 185 megabecquerels (5 millicuries) of iodine-131 sodium iodide to a patient resulted in her 4.2.4.2 External Dose breast-fed infant receiving an unintended radiation dose of 300 grays (30,000 rads) to the infant's To determine a realistic estimate of the external thyroid gland. This dose would result in ablation dose to total decay to the infant during breast of the infant's thyroid. This situation was feeding, an occupancy factor must be selected thatrecognized in 2 days, which allowed prompt action specifically reflects the variables involved. It can to be taken thereby reducing potential be assumed that the average infant feeds for a consequences such as mental retardation. The period lasting 30 minutes every 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br />, resulting NRC is aware of two other cases that occurr in an occupancy factor of 16 percent. Breast- during 1991 and 1995. In each of these cases, feeding requires close contact, the analysis uses there was a breakdown in communications, rather 20 centimeters as the distance between the than infant lack of intent to preveo: breast-feeding. This and the source. Also, since only the physical rule might therefore be expected te provide a
, half-life is considered, the analysis is conservative. benefit by reducing the probability of a woman The results are shown in Column 4 of Table breast-feeding B.5 an infant after administration of assuming no interruption in breast-feeding. large quantitics of iodine-131.
The final rule requires that instructions, including in some cases, instructions to interrupt or written instructions, on maintaining the doses to discontinue breast. feeding may not be effectively other individuals as low as is reasonably communicated. To deal with this issue, the NRC achievable be given to the retcased patient if the considered a range of options which varied from dose to another individual is likely to exceed NUREG-14C 19
)
l cost for the extreme option is 400 x 7 x $1,000 maintaining the status quo to the extreme option = $2.8 million. In addition, there would be of confining a woman for a period of time after associated costs for providing women with administration of millicurie quantities of instructions and information as to the need for iodine-131 sodium iodide to ensure her milk hos'pital retention. The circumstances of a woman production has stopped. Included within this choosing to ignore the warning that breast-feeding range of options was the option to enhance would cause significant harm to the infant and to communication between the licensee and woman continue to breast-feed are considered to be very regarding instructions to interrupt or discontinue rare. As stated above, NRC is not aware of any '
breast-feeding before the woman is released from instance where this has occurred. Therefore, the the hospital. It is estimated that approximately extreme option was not selected because of the 400* breast feeding women could be administered negative psychological impact to both the woman millicurie amounts of iodine 131 sodium iodideand each infant, as well as the high annual dollar cost.
year for diagnosis and treatment of thyroid disease.
Regarding the preferred option to enhance The option of maintaining the status quo does not communication, although instructions to keep j provide the assurance that instructions will be doses to household members and the public as provided to a breast-feeding woman and could Iow as is reasonably achievable are currently still allow for a breakdown in communciations. required for radiopharmaceutical therapy in As indicated above, the NRC is aware of three 10 CFR 35.315(a)(6), there is no requirement cases of unintended exposure to a breast-feeding specific to the dose from breast-feeding. To child during the last five years. There would be enhance communications, amended 10 CFR 35.75(b) ,
no costs associated with this option. will require licensees to provide guidance on the interruption or discontinuation of breast-feeding At the other end of the range, for the extreme and information on the radonale for following the option, a woman would remain in the hospital guidance. Compliance with the regulation until she stopped producing milk. However, this provides NRC with confidence that the licensee option would result in psychological impacts to will give the instructions to breast-feeding women both the woman and breast feeding infant, by and it is expected that almost all women will requiring them to be physically separated for follow instructions to interrupt or discontinue some period of time, which are not quantified by breast-feeding to protect their children from this analysis. This option was also considered to potentially harmful effects. The NRC is not '
be impractical as it would be difficult for a aware of any instances where instructions were medicalinstitution to separate a woman and given to the woman but she ignored the warning breast-feeding child. That is, this option does not and continued breast-feeding a child. Since the prevent the breast 4ed child from being brought estimated costs per patient for providing into the patient's room, nor does it address the instructions and recordkeeping are $22 and $17, situation of the patient releasing herself against respectively (seo 4.3.1.1 Estimates of the Direct medical advice. Also, to require cessation of Costs of Patient Retention), the estimated costs breast-feeding after administration of iodine-131 for this option would be about $16,000 per year. ;
sodium iodide by hospital retention, or prior to Therefore, the option to enhance communication administration (to avoid hospital retention), l is selected as the preferred option. It should be l
directly impacts the practice of medicine, since it noted that since the extreme option was not would in effect dictate when a treatment could beselected for administrations of millicurie given. It is estimated that each woman would quantities, then it would follow that for microcurie remain in the hospital for an average of 7 days at quantities it would not be cost effective.
a cost of $1,000 per day. The estimated annual 4.2.4.4 Summary of Doses to Ilreast-Feeding Infants
- The number of breast-feeding women was determined as follows: 60,000 patients The dose to the breast-feedinginfant can be administered millicurie quantities of iodine-131 controlled by giving the woman instructions, as sodiam iodide x 0.135 child bearing age x 0.05 required by the revised 10 CFR 35.75, to breast. feeding = 405 patients administered discontinue or to interrupt breast feeding as millicuries of iodine who could be breast-feeding.
'O N U RIM i.1492
a e
appropriate. The decision to require instructions about half as much time near the patient. There i as shown in Column 5 of Table B.5 is based on might also be about four other people who will l both the exter'nal and internal dose to the nursing average about a quarter as much time near the infant. It can be secn from Coluren 4 that for patient as the maximally exposed individual. The !
, some radiopharmaceuticals the external dose from ncn of the collective dose to all these people is i breast-feeding can be a significant part of the total 3 times the dose to the maxunally exposed individual. l dose. The duration of the interruption shown in This situation could represent a typical family and l Column 6 is selected to reduce the maximum dose friends. Of course some patients will spend more l to a newborn infant to less than 1 millislevert time near other people, but other patients will (0.1 rem). spend less. A collective dose of 3 times the dose to the maximally exposed individual is thus a The actual doses that would be received by most reasonable average representation.
infants for the recommended interruption periods shown should be a small fraction of 1 millisievert Finally, as data are not available on the (0.1 rem) due to the conservatism of the analysis. distribution of the quantities of radionuclides The conservative factors are based on: (1) the administered for each therapeutic procedure, the maximum measured level of activity in breast estimates of collective dose for each alternative milk, (2) the longest biological half-life, and are based on the typical activities used within the (3) the lowest body weight (i.e., the newborn). ranges of activities administered and the These factors are explained in Appendix B. maximum activity used for thyroid ablation.
4.2.5 Collective Dose By using the results from Table 4.8 (based on the biological model described bv Equation 4) Tables 4.9, l' To evaluate cach alternative, it is also necessary 4.10, and 4.11 present the estima es of the to estimate not only the dose to the maximally collective doses for Alternatives 1,2, and 3, exposed individual, but also the collective dose to respectively, for therapeutic administrations that other individuals who may be exposed to patients could be affected by the choice of alternative. For i the typical administration of iodine-131 for thyroid j administered radioactive materials. To calculate precisely the collective dose that would be ablation, this analysis uses 1.73 millisieverts l received under any of the alternatives would (0.173 rem) (the maximum likely dose to an require detailed information of a highly diverse individual exposed to a patient assuming no group of patients relative to lifestyles, living hospitalization) as the basis for estimating the ;
arrangements, work environments, social activities, collective doses. This value is the average of the etc. This information does not exist and is four doses calculated for the thyroidal uptake essentially impossible to precisely determine. In fractions that characterize the maj dj of patients place of a precise estimate we have made a rough undergoing thyroid ablation. In a similar manner, estimate of the collective dose per therapeutic the dose from the maximum quantity administered procedure which w believe is adequate for the (2,220 megabecquerels (60 millicuries)), was purposes of this rulemaking, determined to be 3.47 millisieverts (0.347 rem).
For thyroid cancer, this analysis uses 4.2.5.1 Collective Dose to Individuals 1.86 millisieverts (0.186 rem) (assuming no hospitalization) as the basis for estimating the Based on considerations of the written instructions collectiva bes. Implants using iodine-125 are provided patients, the demographics of the patient included because doses to exposed individuals population (see Table 4.3), and time, distance, approach 1 millisievert (0.1 rem). Ilowever, and shiciding factors, we estimate that the palladium-103 implants are not included because collective dose per procedure is 3 times the doses to exposed indhiduals are always less than maximal dose (i.e., the dose to the most exposed I millisievert (0.1 rem).
indhidual). This 3 times factor could occur in the following manner, based upon intuitive in Table 4.9 (Alternative 1), the collective dose assumptions about a typical family and friends. In per procedure was determined in tb 'ollowing addition to the person receiving the maximal dose, manner. It was assumed that all; its would who is likely to be the primary care-provider, remain hospitaliecd until the dose gped to there could be two other people who will average ' millisiesert (0.1 rem). Thus, the do. 'the 21 NUREG-1492
1 I
Table 4.9 Estimates of Collective Dose from Therapeutic Radiolodine Procedures for Alternative 1:
Annual Limit of 1 millisievert (0.1 rem)
Typical Activity Collective Estimated Total Therapeutic Administered Dose / Procedure Procedures Collective Dose Procedure (Milq) (mci) (mSv) (rem) per Year (person Sv (rem))
Thyroid Ablation 49,000 147 (14,700) I
- iodine-131 1,110 (30) 3.0 (03) 2,220m (60) 3.0 1,000 3 (300)
(03)
Thyroid Cancer 10,000 30 (3,000) j
- iodine-131 5,550 (150) 3.0 (03) i 1
Permanent Implant 1,480 2.2 2,000 4.4 (440)
- iodine-125 (40) (0.22)
All Therapeutic Procedures 62,000 184.4 (18.440) ;
"' Maximum activity administered. His analysis assumes that 98 percent of the patients are typically administered 1,110 millisieverts (30 millicuries) and that 2 percent are administered the maximum quantity.
1 l
l 1
Table 4.10 Estimates of Collective Dose from Therapeutic Radiolodine Procedures for Alternative 2:
Limits of 1,110 megabecquerels (30 millicuries) or 0.05 millislevert (5 millirems)/hr ;
\
l Typical Activity Collective Estimated Total Therapeutic Adminidered Dose / Procedure Procedures Collective Dose Procedure (Milq) (mu) (mSv) (rem) per Year (person-Sv (rem))
1 Thyroid Ablation ,
5.2 49,000 255 (25,500) l
- iodine-131 1,110 (30) (0.52) 2,220m (60) 9.0 1,000 9 (900) I (0.9)
}
I Thyroid Cancer 5,550 (150) 3.0 (03) 10,000 30 (3,000)
- iodine-131 Permanent implant 1,480 2.2 2,000 4.4 (440)
- iodine-125 (40) (0.22)
All Therapeutic Procedures 62,000 298.4 (29,840)
"' Manimum *ctivity administered. His analysis assumes that 98 percent of the patients are typically administered 1,110 millisieverts (30 millicunes) and that 2 percent are administered the maximum quantity.
NUlW(i-14'12 22
l ,
l.
Table 4.11 Estimates of Collective Dose from 'Iherapeutic Radioiodine Procedures for Alternative 3:
Annual IJmit of 5 millisleverts (0.5 rem)
Typical Activity Collective Estimated Total Therapeutic Administered Dose /Proctdure Procedures Collective Dose i Procedure (Milq) (mci) (mSv) (rem) per Year (person-Sv (rem))
Thyroid Ablation
- iodine-131 1,110 5.2 (0.52) 49,000 255 (25Jn0) -
(30) 2,2205 (60) 10.4 (1.04) 1,000 10.4 (1,040)
Thyroid Cancer
- iodine-131 5,550 5.6 (0.56) 10,000 56 (5,600)
(150)
Permanent Implant
- iodine-125 1,480 2.2 (0.22) 2,000 4.4 (440)
(40)
All Therapeutic Procedures 62,000 325.8 (32,580)
- Maximum activity administered. This analysis assumes that 98 percent of the patients are typically administered I,110 millisieverts (30 mitlicuries) and that 2 percent are administered the maximum quantity.
most exposed individual is 1 millislevert (0.1 rem). is 3 millisleverts (0.3 rem). The collective dose is For iodine-125 implants, the dose is already less 3 times the individual dose or 9 millisieverts than 1 millisievert (0.1 rem) so no hospitalization (0.9 rem). The collective dose per procedure for is required. The collective dose per procedure is iodine-125 implants was calculated similar to that then assumed to be 3 times the dose to the most ' for the typical activity administered for thyroid exposed individual. ablation. For thyroid cancer, an administration of 5,500 megabecquerels (150 millicuries) requires Under Alternative 1, patients administered the about I day of hospitalization to allow the ;
retained activity to reach the release limit. Upon j typical and maximum quantities of iodine-131 for release, the estimated dose to the maximally j thyroid ablation require about 7 and 14 days of exposed individual is 1 millislevert (0.1 rem). !
hespitalizatim respectively, before release can be authorized. Whereas, thyroid cancer patients Therefore, the collective dose is 3 millisieverts administered the typical quantity of iodine-131 (0.3 rems).
require about 1.5 days of hospitalization.
In Table 4.11 (Alternative 3), based on the in Table 4.10 (Alternative 2), the collective dose biological model described by Equation 4, the per procedure was evaluated in th; following collective per procedure was determined in manner. For thyroid ablations using the typical the followwg manner, For thyroid ablation, activity of iodine 131, no hospitalization is required patients administered the typical or maximum since the activity is equal to the release limit of activity can be released immediately because the 1,110 megabecquertis (30 millicuries). The dose from each activity is less than 5 millisieverts collective dose is 3 times the individual dme (i.e., (0.5 rem). The individual doses from the typical ,
and maximum activities are 1.73 millisieverts l 1.73 millisieverts (0.173 rem)) or 5.2 millisieverts (0.52 rem). On the other hand, patients (0.173 rem) and 3.47 millisieverts (0.347 rem), i administered the maximum activity require about respectively. Thus, the collective dose is 1 day of hospitalization before release can be 5.2 millisieverts (0.52 rem) for the typical activity authorized. When released, the maximum dose and 10.4 millisieverts (1.04 rem) for he maximum l
from these patients will be greater than the dose activhy. The collective dose per procedure for l iodine 125 implants was calculated in the same from a patient administered 1,110 megabecquerels (30 millicurica) due to biological considerations. manner a.ssuming no hospitalization. For thyroid The estimated dose to the most exposed individual cancer, administrations of 5,500 megahecquerets 21 NU R EG.1492
(150 millicuries) require no hospitalization In the analysis that follows, these costs are because the dose to the maximally exposed calculated assuming that au retained patients will individual is 1.86 millisieverts (0.186 rem). The be hospitalized. While retention costs reight be less for non hospitallocations, no attempt is made collective dose is 5.6 millisieverts (0.56 rem).
in this analysis to quantify the potential costs.
4.2.5.2 Collective Dose to Hreast-Feeding infants 4.3.1.1 Estimates of the Direct Costs of Patient ;
The dose to the nursing infant from breast- Retention feeding can be controlled to less than 1 milli-Durations of Patient Retention i sievert (0.1 rem) by giving the woman instructions to cease or to interrupt breast feeding (see Section 4.2.4.4 Summary of Doses to Breast- Estimates of the periods of hospitalization that I
Feeding Infants). The actual doses that would be patients would need to remain under licensee received by most infants after interruption should control for each alternative were discussed in be a small fraction of 1 millislevert (0.1 rem) or Section 4.2.5.1 Collective Dose to Individuals.
nothing in the case of cessation. Consequently, Table 4.12 summarizes the duration of retention there is no reason to calculate the collective dose per therapeutic procedure.
to nursing infants from breast feedmg smce it does not affect the choice of alternative. Cost of Patient Retention T estimate the annu 1 a liar e sts for these j 4.3 Value Impact Analysis periods of retention, one needs only multiply the number of days required for each procedure by the number of procedures per year and the 4.3.1 Estimates of the Potential Costs average cost per day of hospitalization. In 1990, the average cost per day in a community hospital The analysis in Section 4.2 indicates that the was $687 (SA92). The per diem cost at the 1 millisievert (0.1 rem) per year dose limit beginning of 1995 is estimated to be $800.
imposed by Alternative 1 would result in the llowever, as the current regulations require that smallest collective dose to individuals exposed to patients who are hospitalized due to a therapeutic released patients. The benefit of smaller doses administration of radiopharmaceuticals be placed estimated for Alternative I will only be achieved if in a privau mom, the $800 per day estimate is the patients '.a whom the radioactive mate.. . adjusted to $1,000 per day. Using this figure, the have been administered are retained under the p tential cost of retaining patients under control of licensees for longer periods of time.
Alternative 1 is estimated to be $427 million.
The impact of retaining patients must be assessed Under Alternative 2, the estimated cost is in terms of the patient, family, and society as a $16 million. And, under Alternative 3, there is no 1
whole. At a minimum, the economic cost must related cost because hospitalization is not conr.ider the direct cost of medical resources required.
required to retain the patient in a hospital and the indirect cost resulting from the loss of human Estimates of the Numbers of Breast-Feeding resources. Additional consideration should be Women Requiring Records and Instructions given to the psychologicalimpact of retention on the affected individual and family members. Under Alternative 3 l
llospitalization will also cause an increase in the '
dose to the hospital kaff and other patients in the The rule associated with Alternative 3 establishes additional requirements for recordkeepine :nd hospital. However, the increase in dose to the hospital staff is expected to be low relative to a providing instructions. Before one ca" etermine the costs of these requirements, it is necessary to patient going home earlier because of the calculate the number of patient releases invohing precautions taken during hospitalization; breast. feeding women that apply to each e.g., patients are isolated and the hospital staff rarely enters the patient's room. requirement.
NUREG 1492 24
I i
l l
Table 4.12 Duration of Retention per Therapeutic Procedure Alternative 1 Alternative 2 Alternative 3 (days) (days) (days) .
Typical Activity hospital total hospital total E Therapeutic Administervd days per hospital days per hospital days per procedures Procedure (MBq) (mCl) procedure days procedare J p -- procedure (x 1000)
Thyroid Ablation l 4
1-131, 50,000 procedures / year 1,110 (30) 7 343,000 0 0 0 0 2,220"> (60) 14 14,000 1 1,000 0 0
- Thyroid Cancer I-131, 10,000 procedures / year 5,5'i0 (150) 1.5 70,000 1.55 15,000 0 0 Permanent Implant, 1-125, 2,000 procedures / year 1,480 (40) 0 0 0 0 0 0 i
Total for All Therapeutic 427,000 16.000 0 Procedures
- Maximum activity administered. This analysis easume. .a* 1 res.en. of de patioc- , typically adr .inistered 1,110 millisieverts j i
(30 millicuries) and that 2 percent are administered the maximum activity, l
- %e analysis under Se-tion 4.2.5.1 Collective Dor- te kdividuals shows I day of hospitalization. Ilowever, patients are typically hospitalized for 1 to 2 days, nus, the actual observed value is shown. l I
I 1
25 NUREG 1492
The number of releases involving breast-feeding imposes additional costs for providing instructions, women that require instructions under including written instructions, on the estimated Alternative 3 is calculated in the following 1,350 licensees, in the case in which the manner. First, the total number of administered activity could cause a dose from administrations potentially requiring instructions direct radiation exceeding 0.1 rem (1 millisievert),
for breast-feeding, approximately 4 million, was instructions would have to be given to 62,000 determined by summing up the number of patients per year at a cost of $1.4 million per year.
administrations for all of the radionuclides in In addition, instructions would have to be given to Table 4.2 that would require instructions based on' approximately 27,000 breast-feeding women at a Table B.5. For radiopharmaceuticals not cost of $0.6 million per year. In both cases, a cost identified in Table 4.2 but listed in Table B.5, the of $22 per patient is estbnated. The total estimated cost ofinstructions is $2 million per year.
number of administrations was assumed to be negligible. Next, from Table 43 it was estimated that 13.5 percent of the radiopharmaceuticals are Costs of Providing Recordkeeping administered to females of childbearing age and Alternatives 1 and 2 have no recordkeeping that 5 percent of them, based on information in Statistical Abstracts of the United States (SA94), requirements, and therefore, have no related could be breast-feeding (assuming an average costs. However, the nde associated with breast feeding period of 1 year). To estimate the Alternative 3 imposes additional paperwork and number of releases that require instruction, one recordkeeping requirements on the estimated needs only multiply 4 million by 13.5 percent, and 1,350 licensees (NRC- and Agreement State-then by 5 percent. Thus,27,000 releases of licensed) that provide diagnostic and therapeutic breast-feeding women require instructions. administrations of radiopharmaceuticals. For therapeutic administrations where releases are not The number of patient releases involving breast- based on the default table of activities and dose ,
feeding women that require a record of rates in Regulatory Guide 839,
- Release of l
~
l instructions under Alternative 3 was calculated in Patients Administered Radioactive Materials" '
the following manner. Using Table B.5, only the (NRC97), a record must be maintained for 3 years.
rdiopharmaceuticals resuhing in a dose to the breast-feeding infant exceeding 5 millisieverts Additionally,if the released patient is a breast-(0.5 rem) with no interruption were identified. Of feeding woman and the radiation do.e to the the identified radiopharmaceuticals, only those nursing infant could result in a total effective dose with a significant number of administrations using equivalent exceeding 5 millisievert (0.5 rem) th.: c':da in Table 4.2 /ere considered. Based on assuming no interruption of breast-feeding, then a this analysis, the total number of administrations record must be maintained, for 3 years, that potentially requiring records for issuance of instructions were provided. In this case, both breast-feeding instructions was estimated at diagnostic and therapeutic administrations of 1.06 million (i.e.,60,000 iodine-131 administrations radiopharmaceuticals could require a record.
for thyroid cancer and ablation plus 1 million technetium-99m pertechnetate administrations), it is estimated that approximately As discussed above,13.5 percent of the 17,200 procedures per year would be subject to radiopharmaceuticals are administered to females these requirements (i.e., (1) 10,000 patients of childbearing age cod 5 percent of them could treated with iodine for thyroid cancer and be breast-feeding. To estimate the number of (2) 7,200 administrations to breast-feeding releases that require a record, one needs only women). A cost of $17 per patient is estimated.
multiply 1.06 million by t3.5 percent, and then by This results in an annual estimated cost of 5 percent. Thus,7,200 releases of breast-feeding approximately $03 million.
women require a record.
43.1.2 Derisation of Indirect Costs Costs of Providing instructions Loss of Time Alternatives 1 and 2 have no requirements for instructions, and therefore, have no related costs. Indirect costs principally reflect the time and flowever, the rule asst.ciated with Alternative 3 output lost or forfeited by the patient while NilRIh lw2 26
1 l
h me -a e Table 4.13 Annual Attributes of Alternatives I,2, and 3 l Cost Estimates llospitalization Value of Records &
Ilospital cost lost time Instructions Psychological Retention 5 $ $ cost i Collective Dose '
Alternative (person-rrm) ~ (uays) ^* - (millions) (millions) (millions) (relative) 18,400 427,000 427 25.62 0 High 1
2 29,840 16,000 16 0.96 0 Moderate l 3 32,580 0 0 0 23 14w l retained in a controlled environment. Indirect the direct and indirect economic costs identified costs may also be incurred by individuals other above. The wide variety of deterioration in the than the patient who may forgo economic quality of life brought on by illness is frequently activities to accommodate a family member's referred to as psychological costs. For thyroid hospital retention. Economic activities include cancer or dysfunction requiring therapeutic doses occupational work that is lost to either the patient of iodin: 131 for example, a deterioration in the or his or her employer as well as non-occupational quality of life may be precipitated by the loss of (e.g., domestic) work which must be performed by bodily function, a lifetime dependence on someone else at the expense of the patient. medication, hormonal instability, uncertainty of normallife-expectancy, disruption of normal daily The conversion of time lost from economic routines, and reduced financial security related to activities to equivalent dollars is most fairly employment, lost earnings, and medical expenses.
achieved by means of the gross national product While some of these elements of psychological (GNP). The GNP is considered the most comprehensivc measure of the country's economic costs are the result of the disease itself, others activity and includes the market value of all goods such as disruption of normal routines, social and services that have been bought for final use isolation, and enhanced financial strain are clearly during a year. From the GNP of about elements of psychological costs that are directly I
$5,600 billion in 1991, the gross average annual related to patient retention. The conversion of l
per capita income of about $22,000 is derived- psychological cost from patient retention to i
The value of $22,000 per year corresponds to equivalent dollars is complex such that an evaluation is highly subjective and dependent upon !
$60 per day. To estimate the equivalent dollar the indiidual situation. Instead, this analysis uses !
value for the number of days lost due to retention of an individual for a therapeutic procedure, one a qualitative and reasonable approach to scope l need only multiply $60 by the days of retention the range of possible responses. As shown in for the procedure presented in Table 4.12. The Table 4.13, comparison is provided on a relative value of the days lost for each alternative is shown scale.
in Table 4.13.
4.3.2 Costs and Benefits of Alternatives 4.3.1.3 Evaluation of Psychological Costs Table 4.13 summarizes the data pertaining to the Retention of patients in a hospital by design necessitates that the patient be " isolated" and that annual attributes for cach of the three alternatives human contact, inclusive of family members,is under consideration. To determine the preferred either avoided or minimited. Such isolation may alternative, the costs and benefits that result when Alternatives 1 and 3 are each compared with bring about numerous changes and impositions in the lives of the patient and f amily members that Alternative 2 (the status quo) were analyzed. The results are shown in Table 4.14. A value of $2,000 may in part be linked to, but are not reflected in 27 NUREG.1492
Table 4.14 Annual Costs and llenefits of Alternatives 1 and 3 Compared to Alternative 2 (He Status Quo)
Collective-Dose'" Costs .
Associated llospitalization, Lost 'Ume, Value Records and lustrurfions Net Benefit Dose Aveded $ $ $
Alternative ' (person-remJ
~~
(millions) (millions) (millions) 1 11,440 (savings) 23 (savings) 435 (cost) -412 (act cost) 2 0 0 0 0 3 -2,740 (cost) -14 (savings) 9 (act savings)
-5 (cost)
- A value of $2,000 per person-rem was used as the conversion factor for Jose averted.
per person-rem was used as the conversion factor to radiation is not expected to result in doses above 1 millislevert (0.1 rem) for long periods of for dose averted (NRC95).
time. The recommendations of the ICRP and Because the benefits and costs for all alternatives NCRP are based on their finding that annual occur in the same year, and remain the same each doses in excess of 1 millisievert (0.1 rem) to a year for the therapeutic procedures discussed, a small group of people, provided that they do not discounted flow of the benefits and costs of this occur often to the same group, need not be rulemaking is not required. regarded as especially hazardous. Although the risk is potentially greater under Alternative 3, it is still within the range of acceptable risk for radiation exposure accepted by the NRC (as 4.4 Evaluation of the Alternatives implemented under the revised 10 CFR Part 20).
With Respect to Accepted Radiation Protection Principles 5 DECISION RATIONALE Selection of the 5-millisieverts (0.5-rem) total effective dose equivalent per year criterion is consistent with: the Commission's provision in 1. All of the alternatives are acceptable 10 CFR 20.1301(c) for authorizing a licensee to according to generally accepted radiation operate up to this limit; the recommendations of protection principles, such as those expnssed the International Commission on Radiological by NRC, NCRP, and ICRP (see Sectiou 4.4 Protection (ICRP) in ICRP Publication 60, "1990 Evaluation of the Alternatives With Respect Recommendations of the International Commission to Accepted Radiation Protection Principles).
on Radiologic d Protection"; and the recommendations of the NCRP in NCRP Report 2. Alternative 1 is considerably more expensive No.116, " Limitation of Exposure to lonizing to the public compared to Alternative 2 (the Radiation." Each of these provide a basis for status quo) or Alternative 3. Even neglecting allowing individuals to receive annual doses up to the psychological costs, which have not been 5 millisieverts (0.5 rem) under certain expressed in dohar terms, the additional cost circumstances. Both ICRP and NCRP of Alternative 1 relative to Alternative 2 is recommend that an individual be allowed to about $412,000,000 per year, mostly due to receive a dose up to 5 millisieverts (0.5 rem) in a increased national health care costs. In view given year in temporary situations where exposure of this, Alternative 1 may be dismissed.
NtJ RiiG- 1492 28
l l
- 3. Alternative 3 relative to Alternative 2 has a administered to a patient, it may be possible l net value of about $9,000,000 per year, mostly to give all of the activity in a single due to lower health care costs. Also, administration. This would reduce the ,
l Alternative 3 has psychological benefits to potential for repeated exposures to hospital l
patients and their families. Thus, staff and to those providing care to the Alternative 3 is cost effective in comparison released patient. Additionally, this would j l '
with Alternative 2. provide physicians with the flexibility to not have to fractionate doses to avoid i i
4 Basmg (ne p46ch release criteria in hospitalization to meet the current 10 CFR 35,75 on the dose to individuals requirements, whi:5 y 926 a more exposed to a patient provides a consistent, effective treatment.
scientific basis for such decisions that treats 1 all radionuclides on a risk-equivalent basis. 6. Shorter hospital stays provide emotional l The dose delivered by an initial activity of benefits to patients and their families.
1,110 megabecquerels (30 millicuries) or a Allowing earlier reunion of families can ,
dose rate at 1 meter of 0.05 millisievert improve the patient's state of mind, which in l (5 millirems) per hour varies greatly from one itself may improve the outcome of the !
radionuclide to another. Thus, while the treatment and lead to the delivery of more values in the current 10 CFR 35.75 may he effective heal:b care.
appropriate for iodine-131, they are too nigh j j
for some other radionuclides and too low for others. 6 IMPLEMENTATION I
- 5. A dose-based rule no longer restricts patient release to a specific activity, and therefore would permit the release of patients with No impediments to implementation of the activities that are greater than currently recommended alternative have been identified.
allowed. This is especially true when case- The staff has prepared a regulatory guide specific factors are evaluated to more (NRC97) for licensees which provides, in part, accurately assess the dose to other individuals. simple methods to evaluate the dose to the For the case of thyroid cancer, in those individual member of the public likely to receive occasional cases where multiple administrations the highest dose from the released patient. This in a year of 1,110 megabecquerels will enable licensees to determine when a patient (30 millicur:es) or less of iodine-131 are now may be released from their control.
l l
29 NUREG-1492
i J
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l l .-
l r
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IJ l
I NUR EG.1492 34
1
. I l
l l
l i
l APPENDIX A PARAMETERS AND CALCULATIONS FOR DETERMINING '
l RELEASE QUANTITIES AND DOSE RATES FOR '
RADIONUCLIDES USED IN MEDICINE
~~
Table A 1 Italf-Lives and Exposure Rate Constants of Radionuclides Used in Medicine
- mamme Exposure Exposure Half-Life Rate Constant llalf-Life Rate Constant (days) Radionuclide (days) (R/ mci-b at I cm)
Radionuclide (R/mO h at 1 on) 0.13 Pd-103 implant 16.96 1.48 "
Ag-111 7.45 Re-186 3.777 0.168 Au-198 2.6% 2.3 Re-188 0.708 0.26 Cr-51 27.704 0.16 1 l
1.2 Sc-47 3351 0.56 Cu-64 0.529 l Se-75 119.8 2.6 Cu-67 2.578 0.58 Sm-153 1.946 0.425 Ga-67 3.261 0.753 Sn-117m 13.61 1.48 I-123 0.55 1.61 1.42 Sr-89 50.5 NA' 1-125 60.14 Tc-99m 0.251 0.756 I-125 implant 60.14 1.11' TI-201 3.044 0.447 1-131 8.04 2.2 3.21 Y-90 0.133 NAt In-111 2.83 Yb-169 32.01 1.83 Ir-192 implant 74.02 4.59' P-32 14.29 NA'
- References for half-lives and exposure rate constants are shown in Table A-2.
" A. Meigooni, S. Sabnis, and R. Nath,
- Dosimetry of Palladium-103 Brachytherapy Sources for Permanent implants
- Endocurietherapy Hyperthermia Oncology, Volume 6, April 1990. The exposure rate constan is an " apparent" value (i.e., with respect to an apparent source activity) and takes into account the attenua of gamma rays within the implant capsule itself.
- R. Nath, A.S. Meigooni, and J.A. Meli, " Dosimetry on Transverse Axes of $1 and "Ir Interstitial lirachytherapy Sources," MedicalPhysics, Volume 17, Number 6, November / December 1990. The exposure rate constant given is a measured value averaged for several source models and takes into account the atte of gamma rays within the implant capsule itself.
' Not applicable (NA) because the release activity is not based on beta emissions.
NOTE: Information on non. byproduct material is included for the convenience of the license.
l A.1 N U REG.1492
t Table A-2 Exposure Rate Constants, Release Activities, and Release Dose Rates 3
- E Release Activity Based On Release 2 Dose Rate E Linear Energy- Exposure Rate 0.5 rem to Total Decay Absorption at 1 Meter i Intensity
- R/Ci-hr R/ mci-hr Q Q. Q for Q IIalf-Life " (fraction / Energy
- Coefficient t* MeV/cm/
disintegration at 1 Meter at I c m (mci) (MBq) (GBq) (mrem /hr)
Isotope (days) disintegration) (MeV) (1/m) 4J0E-02 2.42E-09 3.63E-05 3.63E-04 Ag-111 7.45 0.000245 0.022984 4.00E-02 4.28E-09 6.42E-05 6.42E-04 0.000462 0.023174 1.65E-04 0.0261 2.80E-02 1.10E-09 1.65E-05 0.000151 5.23E-04 (Occupancy Factor = 0.25) 0.09675 3.00E-03 3.49E-09 5.23E-05 0.001202 1.6%E-02 0.24539 3.60E-03 1.09E-07 1.63E-03 0.012291 1.30E-01 l 0.34213 3.80E-03 8.68E-07 130E-02 0.0668 2.09E-03 0.65472 3.80E-03 139E-08 2.09E-04 0.000559 1.50E-01 5.17E +02 1.91E + 04 1.91E + 01 7.76E + 00 Exposure Rate Constant (Total)* 1.50E-02 (Omyancy Factor = 0.25)
Au-198 2.696 Exposure Rate Constant" 230E-01 2J0E + 00 932E+01 3.45E + 03 3.45EIO0 2.14E + 01 (Occupancy Factor = 0.25) b Cr-51 27.704 1.60E -01 130E + 02 4.81E + 03 4.82E + 00 2.09E + 00 Exposure Rate Constant" 1.60E -02 (Occupancy Factor = 1.0)
Cu-64 0.529 Exposure Rate Constant" 1.20E-01 1.20E + 00 2.28E +02 8.42E + 03 8.42E + 00 2.73E + 01 (Occupancy Factor = 0.25)
Cu-67 2.578 5.80E-01 3.87E + 02 1.43 E + 04 1.43 E + 01 2.24E + 01 Exposure Rate Constant"* 5.80E-02 3.00E-03 7.82E-08 1.17E-03 1.17E-02 Ga-67 3.261 0.02856 0.09!266 2.95E-03 9.83E-07 1.47E-02 1.47E-01 0.357 0.093311 3.40E-03 1.24E-06 1.85E-02 1.85E-01 0.19706 0.18458 (Occupancy Factor = 0.25) 3.50E-03 1.64E-07 2.46E-03 2.46E-02 0.02242 0.20895 3.75E-03 1.80E-06 2.70E-02 2.70E-01 0.15994 0.30022 3.90E-03 6.87E-07 1.03E-02 1.03E-01 0.044768 0 39353 3.65E-03 4.49E-08 6.73E-04 6.73E-03 0.001385 0.88769 3.85E-03 3.02E-08 4.53E-04 4.53E-03 0.001247 0.62941 Exposure Rate Constant (Total)* 7.53E-02 7.53E-01 2.35E + 02 8.71E + 03 8.71E + 00 1.77E + 01
Table A-2 Exposure Rate Constants, Release Actinties, and Release Dose Rates (Continued)' __
Release Activity Based On Release 0.5 rem to Total Decay Dose Rate L.mear Energy- Exposure Rate at 1 Meter Intensity 8 Absorpten 8 Coefficient 88 MeV/cm/ R/Ci-br R/ mci-hr Q 4 4 for Q IIalf-Life" (fraction / Energy (MBq) (GBq) (mrem /hr) disintegration at 1 Meter at I cm (mci)
Iwtope (days) disintegration) (MeV) (1/m)
(Occupancy Factor = 1.0) .
1-123 0.55 1.61E + 00 1.63E + 02 6.04E + 03 6.34E3 00 2.63 E + 01 Exposure Rate Constant *" 1.61E-01 2.77E-06 4.16E-02 4.16E-01 60.14 0 39233 0.027202 2.60E-02 1-125 5.03E-06 7.54E-02 7.54E-01 (Occupancy Factor = 0.25):
0.73196 0.027472 2.50E-02 i e 1.73 E-02 I J6E-06 2.04E-02 2.04E-01 0.25409 0.031 e 1.20E-02 2.76E-07 4.14E-03 4.14E-02 0.0649 0.035492 1.42E + 00 6.77E + 00 2.50E + 02 2.50E-01 9.61E-01 Exposure Rate Constant (Total)* 1.42E-01 (Occupancy Factor = 0.25) 1-131 8.04 2.20E +00 3.27E + 01 1.21E + 03 1.21E + 00 7.19E + 00 Exposure Rate Constant
- 2.20E-01
> (Occupancy Factor = 0.25)
- In-l i t 2.83 Exposure Rate Constant"* 3.21E-01 3.21E + 00 636E+01 235E+03 2.35E + 00 2.04E + 01 (Caspg Factor = 0.25)
Ir-192 74.02 4.80E + 00 1.63E + 00 6.02E +01 6.02E-02 7.81E-01 Exposure Rate Constant" 4.80E-01 6.20E-02 3.57E-06 535E-02 SJ5E-01 16.96 0.2866 0.02007 1.01E +00 N 103 6.10E-02 6.71E-06 1.01E-01 0.5443 0.02022 3.45 E-01 (Occupancy Factor = 0.25) 6.00E-02 2J0E-06 3.45 E -02 0.169 0.02272 6.02E-05 3.80E-03 4.02E-10 6.02E-06 0.00003 0.3524 2.09E-04 3.90E-03 1.40E-09 2.09E-05 0.00009 03975 1,45E-05 3.90E-03 9.69E-11 1.45E-06 0.000005 0.4971 _
1.89E-01 1.89E + 00 1.80E +01 6.67E + 02 6.67E-01 3.41E + 00 Exposure Rate Constant (Total)*
Z.
C I
tJ
x Table A-2 Exposure Rate Constants, Release Activities, and it. lease Dose Rates (Continued)*
3 Release Release Activity Based On Dose Rate 5 Linear Energy
- Exposure Rate 0.5 rem to Total Dc:ay at 1 Meter Intensity 8 Absorpten for Q, c R/Ci-hr R/ mci-hr Q, Q. C.
" Energy
- Coefficient " MeV/cm/
llatf-Life" (fraction / disintegration at 1 Meter at I cm (mci) (MBq) (GIq) (mrenv'hr)
Isotope (days) disintegration) (MeV) (1/m) '
3.90E-08 5.84E-04 5.84E-03 0.016 0.058 4.20E -03 Re-186 3.777 6.59E-08 9.89E-04 9.89E-03 O.0278 0.0593 4.00E-03 2.85E-08 4.28E-04 4.28E-03 0.0118 0.0672 3.60E-03 2.65E-OS 3.98E-04 3.98E-03 0.007 0.1223 3.10E-03 (Occupancy Factor = 0.25) 2.78E -08 4.17E-04 4.17E-03 0.0116 0.0615 3.90E-03 4.85E-07 7.27E-03 7.27E-02 0.02 0.063 3.85E-03 2.12E-08 3.18E-04 3.18E-03 0.0086 0.0714 3.45E-03 4.11E-07 6.17E-03 6.17E-02 0.0952 0.1372 3.15E-03 1.60E-08 2.40E-04 2.40E-03 0.0006 0.7022 3.80E-03 1.68E-01 9.11E +02 3.37E +04 337E+01 1.53E + 01 Exposure Rate Constant (Total)* 1.68E-02 (Oecupancy Factor = 1.0)
Re-188 0.708 2.60E-01 7.85E + 02 2.01E + 02 2.91E + 01 2.04E + 01 Exposure Rate Constant'" 2.60E-02 (Occupancy Factor = 0.25)
Sc-47 3351 1.72E + 0!
5.60E -01 3.08E + 02 1.14E + 04 1.14E +01 Exposure Rate Constant" 5.60E -02 (Occupancy Factor = 0.25)
Se-75 119.8 4.82E-01 2.60E + 00 1.86E +00 6.87E + 01 6.87E-02 Exposure Rate Constant" 2.60E-01 5.44E-07 8.15E-03 8.15E-02 0.17263 0.040902 7.70E-03 Sm-153 1.946 9.47E-07 1.42E-02 1.42E-01 0.31218 0.041542 730E-03 2.64E-07 3.96E-03 3.96E-02 0.12217 0.047 4.60E-03 1.24E-07 1.86E-03 1.86E-02 0.0517 0.069672 3.45E-03 (Occupancy Factor = 0.25) 4.90E-09 735E-05 735E-04 0.00194 0.075422 335E-03 534E-09 8.00E-05 8.00E-04 0.002 0.083366 3.20E-03 4.24E-09 636E-05 636E-04 0.00158 0.089484 3.00E-03 2.10E-08 3.15E-04 3.15E-03 0.00718 0.09743 3.00E-03 8.76E-07 131E-02 1.31E-01 0.283 0.10318 3.00E-03 4.52E-08 6.77E-04 6.77E-03 0.002775 0.42266 3.85E-03 4.23E-02 4.25E-01 6.99E +02 2.59E +04 2.59E + 01 2.9 E+0!
Exposure Rate Constant (Total)* .
O 8
t Table A.2 Exposure Rate Constants, Release Activities, and Release Dose Rates (Continued)' ,
Release Release Activity Based On Dose Rate Linear Energy- Exposure Rate 0.5 rem to Total Decay at 1 Meter Intensity 8 Absorption MeV/cm/ R/Ci-hr R/ mci-hr Q, Q, Q. for Q, Itaff. Life" (fraction / Energy8 Coefficient "
disintegration at 1 Meter at I em (mci) (MBq) (GBq) (mrem /hr)
(days) disintegration) (Mey) (1/m)
Iwtope 335E-02 1.57E-06 2.35E-02 2.35E-01 Sn.117m 13.61 0.1873 0.025 3.30E-02 2.93E-06 4.40E-02 4.40E-01 0.3514 0.0253 7.60E-07 1.14E-02 1.14E-01 (Occupancy Factor = 0.25) 0.1185 0.0285 2.25E-02 3.25E-03 1.07E-07 1.60E-03 1.60E-02 0.0211 0.156 330E-03 4.52E-06 6.78E-02 6.78E-01 0.864 0.1586 1.48E-01 1.48E + 00 2.87E + 01 1.06E + 03 1.06E + 00 4.25E + 00 Exposure Rate Constant (Total)*
7.90E-02 3.03E-07 4.54E-03 4.54E-02 0.251 0.021021 0.018251 Tc-99m 5.83E-07 8.74E-03 8.74E-02 0.040194 0.018367 7.90E-02 1.47E-07 2.20E-03 2.20E-02 (Occupancy Factor = 1.0) 0.012059 0.0206 5.90E-02 3.20E-03 4.00E-06 6.00E-02 6.00E-01 0.8907 0.14051 3.20E-03 9.77E-10 1.46E-05 1.46E-04 0.000214 0.14263 7.56E-01 7.62E + 02 2.82E +04 2.82E + 01 5.76E + 0!
Exposure Rate Constant (Total)* 7.56E-02 1.80E-02 1.21E-08 1.82E-04 1.82E-03 3.044 0.0022 0.0306 TI-201 3.45E-03 6.50E-07 9.75E-03 9.75E-02 0.27357 0.068895 3.40E-03 1.12E-06 1.6SE-02 1.68E-01 0.46525 0.070819 (Occupancy Factor = 0.25) 3.20E-03 5.26E-07 7.88E-03 7.88E-02 0.20465 0.0803 3.20E-03 1.15E-07 1.72E-03 1.72E-02 0.0265 0.13534 330E-03 8.76E-09 131E-04 1.31E-03 0.0016 0.16588 330E-03 5.53E-07 8.28E-03 8.28E-02 0.1 0.16743 4.47E-02 4.47E-01 4.25E +02 1.57E +04 't .57E + 01 1.90E + 01 Exposure Rate Constant (Total)*
7 .
C E -
'S I
IJ
i 1
l 2
Table A-2 Exposure Rate Constants, Release Activities, and Release Dose Ratea (Continued)t 5 Release Activity Based On Release 5 L,near Energy-i Exposure Rate 0.5 rem to Total Decay Dose Rate g Absorption at 1 Meter 2 Intensity *
" Energy
- Coefficient ** MeV/cm/ R/Ci-hr R/ mci-hr Q, Q. Q. for Q, Half. Life" (fraction / at I cm (mci) (MBq) (GBq)
(1/m) disintegration at 1 Meter (mrem /hr)
Isotope (days) disintegration) (MeV) 0.02075 6.00E-02 2.66E-08 3.98E-04 3.98E-03 Yb-169 32.01 0.002134 5.25E-03 1.38E-06 2.07E-02 2.07E-01 0.52777 0.049773 5.05E-03 2.39E-06 3.59E-02 3.59E-01 0.93411 0.050742 4.25E-03 9.36E-07 1.40E-02 1.40E-01 0.38301 0.0575 3.75E-03 1.04E-06 1.55E-02 1.55E-01 0.43747 0.063119 3.05E-03 7.59E-08 1.14E-03 1.14E-02 -
0.026578 0.093613 3.05E-03 5.81E-07 8.72E-03 8.72E-02 0.17363 0.10978 3.10E-03 6.89E-08 1.03E-03 1.03E-02 (Occupancy Factor = 0.25) 0.018818 0.11819 3.20E-03 4.62E-07 6.92E-03 6.91E-02 0.11058 0.13052 3.40E-03 1.29E-06 1.94E-02 1.94E-01 0.21437 0.17721 :
3.60E-03 2.49E-06 3.73E-02 3.73E-01 0.3492 0.19795 e 3.60E-03 1.06E-08 1.59E-04 1.59E-03 0.001222 0.2403 3.65E-03 1.68E-07 2.52E-03 2.52E-02 0.017654 0.26107 3.75 E -03 1.25E-06 1.87E-02 1.87E-01 0.10806 0.30773 I 3.80E-03 2.41E-08 3.61 E-04 3.6] E-03
~
0.001843 0.34406 Exposure Rate Constant (Total)* 1.83E-01 1.83E + 00 9.87E+ 00 3.65E + 02 3.65E-01 L81E + 00
' Values shown for the exposure rate constant, release activity, and release dose rate for each isotope are based on a bare point source, no shielding considered.
" K F Eckerman, A.B. Wolbarst, and A.C.B. Richardson,
- Federal Guidance Report No.11, Limiting Values of Radionuclide intake and Air Concentration Office of Rad iation Programs, U.S. Env ironmental and Dose Conversion Factors for Inhalation, Submersion, and Ingestion," Report No. EPA-520/1-88 020, Protection Agency, Washington, DC,1988.
- Val es for the intensity and energy for Ag-I11, Ga-67, I-125, Sm-153, Tc-99m, TI-201, and Yb-169 were taken from: Bernard Shleien, 7he Health Physi.s.
and Radiological #cahh Hardbook, Revised Edition, Scinta, Inc. 1992, pages 294-334. For Re-186 and Sn-117m, the values for intensity and energy were
- taken f rom: L.M. Unger and D.K. Trubey, " Specific Gamma-Ray Dose Constants lor Nuclides important to Dosimetry and Radiological Assessment," U.S.
A.S. Meigooni and R. Nath, "A Comparision Department of Energy, ORNL/RSIC-45/RI,1932. For Pd-103, the values for intensity and energy were taken:
of Radial Dose Functions for "Pd, WI, '*Sm, "Am, '*Yb, "Ir, and "'Cs Brachytherapy Sources," InternationalJournal of Radiation Oncology-Biology.
I'hysics, Volume 22, Number 5,1992.
" Values for the linear energy-absorption coefficient in air were taken from: Radiologcal Hea!rh Handbook, U.S. Department of Health, Education, and Welfare, page 135, 1970.
t
- The exposure rate constant was calculated because the pubhshed value for this isotope was an approxima'e value, presen r from one reference to another. Only gamma rays and X-ray. with energies 74. heabove exposure113 rate constant kev were used tobycalculate was calculated using the exposure rate ,.
cutoff is the one used in NCRP Report No. 41,
- Specification of Gamma-Ray Brachytherapy Sources," 19 ;
the following equabon:
dis 1 Wl** I" 4 E
- **"i g,g )( 4r (100 cm)2 } E p gm em4 #' ( 87.6 erg)(1.6 x 10 MeV ):
p = (1332 x 10
Where E, - the energy of the ith gamma ray or X-ray i, McV.
f, _ = the probabihty of decay (i.e., intensity) of gamma rays or X-rays with energy 5 per disintegration.
= the liccar energy absorption coefficient in air of photons of energy E. / f p,3 t p = the density of air at standard temperature and pressure, taken to be 0.0012929 gm cn .
- Radiologcal Heattit Handbook, U.S. Department of Health, Education, and Welfare,1970.
- D.E. Barber, J.W. Baum, and C.B. Meinhold,
- Radiation Safety Issues Related to Radiolabeled Antibodica,* NUREGICR-4444, U.
Commission, Washigton, DC,1991. >
k k"
- i a
2 C
- c E -
E 5 .
t
. t l
APPENDIX B PARAMETERS AND CALCULATIONS FOR DETERMINING INSTRUCTIONS TJ BREAST-FEEDING WOMEN-B.1 CALCULATIONAL already been made). Then, this maximum
""'**3'"
-l
. . - ******""*d' i METHOD 'post
"*""*9 "tration. It might have been more admtms conservative to extrapolate this back from the time at which the concentration was observed to i
3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br /> post administration, but in many cases, The breast milk concentration of a nly ne value was reported and a biolog, cali radiopharmaceutical as a function of time C(t), :
half-life was not availtble. If concentrations were (i.e., the activity per milliliter of breast milk) was reported at times less than 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br />, the highest calculated from the equation, concentration reported was used without correction for biological removal, and assumed to occur at 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br /> post administration.
C(t) = A aexp(-(A + A,)(t-3)), (B.1)
A computer program was written which used Equation B.1 describing breast milk concentration '
where A = the activ.ity adm.tms . tered to the as a function of time represented by each scenario w asan, to estimate the fraction of the activity administered to the woman which would be excreted in the a = maximum fractionof administered breast milk and ingested by the infant. The activity (per milliliter of breast milk), program assumed that the infant would resume feeding at 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br /> post administration and would h = biological decay constant, then nurse every 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br /> thereafter (i.e.,8 feedings per day), consuming 125 milliliters of milk per X, = physical decay constant. feeding (this represents a daily average consumption of 1,000 milliliters). Thus, the t = time at which breast-feeding occua. program cassia.ated the breast milk concentration (in units of fraction of administered activity per A comprehensive search of the medicalliterature milliliter of milk) at 3 hour3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br /> intervals based on the excretion functions observed, multiplied by was performed in early 1995. From the data gathered from the literature, the highest 125 milliliters to estimate the total fraction concentration (or highest fraction) a2 of a ingested at that feeding, and added up a total radiopharmaceutical in the breast milk post fractional absorption over all feedings (summations administration to the women and the longest were carried out to 50 effective half-lives). The biological half-life T., (not necessarily from the program also calculated cumulative ingestion for same study) were chosen to represent the worst assumed interruption periods of 12 hours1.388889e-4 days <br />0.00333 hours <br />1.984127e-5 weeks <br />4.566e-6 months <br /> (0.5 day) case scenario, and the lowest concentration (or 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> (1 day),48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br /> (2 days),96 hours0.00111 days <br />0.0267 hours <br />1.587302e-4 weeks <br />3.6528e-5 months <br /> lowest fraction) a, and shortest biological half-life (4 days),120 hours0.00139 days <br />0.0333 hours <br />1.984127e-4 weeks <br />4.566e-5 months <br /> (5 days),168 hours0.00194 days <br />0.0467 hours <br />2.777778e-4 weeks <br />6.3924e-5 months <br /> (7 days),
Tuwere chosen to represent the best case scenario. 336 hours0.00389 days <br />0.0933 hours <br />5.555556e-4 weeks <br />1.27848e-4 months <br /> (14 days), and 672 hours0.00778 days <br />0.187 hours <br />0.00111 weeks <br />2.55696e-4 months <br /> (28 days). For Breast milk concentrations reported in the example, if the interruption time was 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br />, the first calculation would have been for r = 24, literature were first corrected for radioactive decay to the time of adminisaation (unless the followed by 27 hours3.125e-4 days <br />0.0075 hours <br />4.464286e-5 weeks <br />1.02735e-5 months <br />,30 hours, and so on. There article explicitly stated that such a correction had is no information in the literature describing
\
'Information in this appendix was provided by R.E. Toohey. M.G. Stabin, and J. Stubbs, Radiation Internal Dose Information Center (RIDIC), Oak Ridge Institute for Science and Education, Oak Ridge, TN.
I Ill NU REG-1492
- i 4 ,
i l
(MO89a). This is probably a conservative upper uptake of ingesteti radiopharmaceuticals from the infant gastrointestinal (GI) tract, thus it was limit in most cases. In those cases in which a assumed that 100 percent of the ingested activity literature reference gave only the cumulative fraction of activity excreted in the breast milk over !
was qmckly and completely absorbed from the the course of the study, the fraction of injectea ,
infant's GI tract, '
activity excreted per milliliter of milk at different times was not available (although a clearance Radiation doses for newborns (3.4 kg) and one- !
half life may have been reported). A single value year-olds (9.8 kg), based on the mathematical -
of cumulative excretion could not be used in this phantoms of Cristy and Eckerman (CR87) have - .J,sL, as it most likely represented the been estimated for the radiopharmaceuticals cumulative fraction excreted assuming no considered in this analysis and compiled in a interruption of breast feeding, and therefore could [
reference on pediatric radiation dosimetry in not be used directly to infer the cumulative nuclear medicine (ST95). These dose estimates fraction under different interruption schedules.
generally apply to intravenous administration of these pharmaceuticals. The dose estimates are To estimate the cumulative fraction under different interruption schedules, it was necessary expressed as effective dose equivalents (EDE) per to calculate the time-dependent behavior of the unit ingested activity; a summary of the values c!carance. Thus, a breast milk concentration at used are given in Table B.I. (Some dose estimates, based on more recent models were early times was estimated which would result in a cumulative excretion equal to the value reported supplied by the Radiation Internal Dose Information Center, Oak Ridge, TN.) Typical assuming no interruption of breast-feeding, the clearance half-life reported by the authors, and ;
values of activity administered to the woman per using the nursing schedule and volume assumed in procedure were taken from various sources, to this analysis. This derived early concentration was estimate the total internal dose to the infant from then used in the computer program with the a typical procedure. There are certainly cases, most notably for therapeutic administrations of clearance half-life chosen to estimate the iodine-131 sodium iodide, in which the effective cumulative fraction ingested under different dose equivalent should not be used for decision interruption schedules.
making, and the individual organ absorbed doses None of the analyses for the iodine compounds should be considered.
included any considerations for free iodide in the The computer program estimated the intab a% phumaceutical product, s hile the other analyses did not include considerations for possible subsequent dose to newborns and one-year-olds for both the best and worst case scenarios, wi .a radioactive contaminants (except for the three cases discussed below) or breakthrough products.
interruption (first feeding 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br /> after administration to the woman), and for the various These additional components of the dose are interruption schedules described above. usually very small. Also,the assignment of i
numerical values to these quantities (the fraction An upper limit of 0.50 was placed on the total of free iodide, percent activity of contaminants, fraction of administered activity which could be etc.) would be arbitrary, as these values vary considerably between products, and even with excreted over all time in the breast milk. It was possible for uarealistic values (e.g., fractions time.
3;reater than 1.0) to be calculated by merely However, the presence of possible radioactive permitting the computer program to sum the contaminants in some of the pharmaceutical product of the fraction of activity per milliliter and 125 milliliter per feeding for a large number of products was considered. The cases considered feedings. Thus,it was thought that an upper limit were: (1) indium-114m and indium 114 of 0.50 should be placed on this value, which contaminants in indium-111 products, represents excretion through the breast milk (2) iodine 125 contaminant in iodine-123 products, pathway competing equally with all other and (3) thallium-200 and thallium-202 contaminants in thallium-201 chloride. Finding cxcretion pathways available. This value is also compatible with the highest fraction reported for published informa'. ion about the possible levels of total excretion of any radiopharmaceutical, namely these contaminants likely to be found in the a fraction of 0.33 for iodine-131 sodium iodie products was difficult. The most common source NL IR EG-1492 H.2
of these data is the radiopharmaceutical package the radiopharmaceuticalin breast milk as inserts. Discussion with some industry experts, described alme (see Section B.1 CAlfULA'110NAL j however, indicated that the levels listed in most of METliOD). When data for a single subject were -
these inserts may considerably overestimate actual reported, the reported / derived value of excretion f levels encountered in current practice. Therefore, frrtion per milliliter of breast milk was the levels adopted for this analysis are those considered to be
- highest", for that publication, and no " lowest
- value was listed. In some cases, j gathered as a consensus of some experts in measuring these quantities. The values used the breast milk peak concentration was estimated i
from graphical information in an article; these were: (1) indium-114m and indium-114 -
0.25 percent, (2)iod'm e-12/; C 0; percent, and estimates are shown with a " " symbol.
(3) thallium-200 - 03 percent and thallium-202 -
1.2 percent. Altho agh the additional dose from Robinson et al. (RO94) reported a concentration l these contamiaants is included in the values in and excretion half-life for a diagnostic dose of l Table B-4, the number of millicuries of activity iodine-131 sodium iodide and also reported that and the percent of administered activity ingested the same patient exhibited biphasic excretion of ;
by the infant in that table reflects only the the iodine-131 administered in a therapeutic study. l i
contribution from the main radiopharmaceutical. Murphy et al. (MU89) reported that thallium-201 chloride exhibited biphasic clearance. All other radiopharmaceuticals seemed to follow mr.nophasic !
clearance Patterns, except for two case audies B.2 RESULTS 1
involving iodine-131 sodium iodide. This !
radiopharmaceutical was nonethelere modeled !
with a monophasic clearance paturn for the This analyses covers 25 of the radiopharmaceuticals purp ses f this study.
most commonly used in nuclear medicine procedures involving women who are breast-feeding an infant. Table B.3 lists the biological and physical '
parameters used by the computer program to calculate the total activity ingested and the B.2.1 Biok.inetic Data for Excret. ion internal radiation doses received from the intake of Radiopharmacueticals in tf radiopharmaceuticals in breast milk for Breast Milk newborns and one-year-olds.
The data obtained from the literature review are summarized in Table h.2. The biokinetic data for B.2.2 Radiation Dose Estimates each radiopharmaceutical excreted in breast milk are given in Table B.2 as the excretion fraction, per unit volume of breast milk, the biological Table B.4 lists the dose estimates for the 25 half-life for excretion, time of peak concentration radiopharmaceuticals analyzed, for both the (when data were reported as concentration rather newborn and the one-year-old, for both best and than cumulative excretion fraction), and the worst case scenarios, and for allinterruption reference. Most papers reported an effective schedules. Note, that in the case of iodine-131 half-life for excretion of radiopharmaceuticals in sodium iodide the infant rhyroid doses, instead (f breast milk and these values were converted to effective dose equivalents, were shown, due to t'.se biological half lives. Several values of the high doses predicted. Table B.5 shows the reported effective half-life for excretion were summary of recommendations for the larger than the physical half-life of the radiopharmaceuticals considered in this analysis, radionuclide (e.g., T,, = 9 hours1.041667e-4 days <br />0.0025 hours <br />1.488095e-5 weeks <br />3.4245e-6 months <br /> for showing the maximum administered activities Technetium 99m RBCS (RU94)) indicating assumed, the internal dose to the infant if no continued accumulation in the breast milk of the interruption of breast feeding is assumed, whether radiopharmaceutical over time. These values are or not instructions are required, the external dose denoted in the table in parentheses. Several from radiation during breast-feeding assuming publications reported cumulative excretion interruption, and the recommendation on interruption fractions (denoted by the symbol 66) and these of breast feeding (which includes adjustment for values were used to estimate the concentrations of the external dose during breast feeding).
H3 NUREG 1492
l l
Table 11.1 EITective Dose Equivalents to Newborns and One-Year-Olds from Infant's intake of Radiopharmaceuticals Eltective Dose Equivalent'" (rem /mCl)
Radiopharmaceutical Newborn One-Year-Old 0.11 0.048 Cr-51 EDTA Ga-67 Citrate 6.7 2.6 5.9 4.1 I-123 miBGS 0.24 0.10 1-123 0111 5.9 4.1 l 1-123 Sodium Iodide (Nal)
I-125 Olli 0.89 036 f
1.1 0.44 1-131 Olli 14,000* l 20,000m I-131 Sodium 1odide (Nal) 33 13 In-111 White Blood Cells 0.85 0.41 Tc-99m DISIDA 0.13 0.056 Tc-99m DTPA 0.28 0.12 Tc-99m DTPA Aerosol 036 0.16 l Tc-99ra Glucoheptonate l
0.56 0.23 l Tc-99m liAM l
0.63 0.26 Tc-99m MAA 0.12 0.052 Tc-99m MAG 3 0.41 0.16 Tc-99m MDP 0.52 0.24 Tc-99m MIBl 0.41 0.19 Tc-99m 0, (Pertechnetate) 0.28 0.12 Tc-99m PYP Tc-99m RBC - In Vitro Labeling 031 0.14 l Tc-99m RBC - In Vivo Labeling 030 0.14 Tc-99m Sulfur Colloid 0.74 036 0.41 0.19 Tc-99m White Blood Cells")
l 15 8.5 l TI-201 Chloride
'" l'ffecove dose equivalent to the infant per unit activity administerted intravenously to the infant (except in the case of Tc 99m DTPA Aerosol).
d' Specificatmn tests indicated that the activity was most likely in the form of Nal, npot mlDG. Thus, the dose estimate for 1-123 mlBG is that shown for 1-123 Nat.
"' Dose to the infant's thyroid per urut activity administered intravenously (or orally) to the infant (rad / mci).
- The values shown are actually the dose estimates for Tc-99m pertechnetate, as it wrs assumed that activity released m breast milk from this product would be in the form of pertechnetate.
NUREG 1492 B.4
I
?e Table !!.2 Excretion Fractions and it;ological IIalf-Lives for Radiopharmaceuticals Excreted in lircast Milk l
l Biological l Ilatf-Life !
Measured for !
Excretion Fractions
- Excretion i Radiopharmaceutical a T (hr) Reference , , ,
Cr 51 EDTA 1.5E-4fl - 6.5E. 05 -
5.0-7.0 AH85 Ga-67 Citrate 9.5E-5 (72) 216 TO76 2.7E-5 (38) - 3.7E-5 (58)82-385 RU94 5.6E-5 (%) LA71 1.0E4 (88) GR83 43E-5 (48) WE94 3.16E-266 - 9.9E 266 20-390 RU94 1-123 mlBG* 7.2E-6 (8) 85 KE94 1-123 OliI 6.0E-5 4.8 M O89b 1.2E-0256 - 3.5E-266 8.1-10.2 RO90 1.5E-4 (4) 83 RO90 2.6E-266 10.4 IIES6 1123 Sodiun todide (Nal) 6.5E-5 10.4 11E86 I-125 0111 2.4E-265 4.8 All85 1131 Olii 1.8E-266 - 4.9E-255 2.2-6.0 AlI85 t
' Sodiun lodide (Nal) 1.4E-5 (24) - 4.0E-5 (6) ~ 9.9 NU52 6.7E-4 (6) WE60 6.6E-4 12 DY88 (2 comp 1.6E-5 526 model) 3.0E-2 (18) - 9.4 RUS8
~5-.0E-4 13 RO94 (diag.) 1 11 RO94 (ther. l 235 2 comp n.odel) i 23E-1%l 117 RU94 I
2.5E-165 - 4.6E 166 7.6-12 M O89a In-111 White Blood Cells 33E-7 (13) (853)tt M O85 7.3E-7 (16) (140)tt iIE88 2.4E 7 (20) BU86 Tc-99m DISIDA 1.0E-356 - 2.8E-366 10-(9.1)tt RU94 l
l 1
l 11.5 NUREG 1492
- l. .
Table 11.2 Excretion Fractions and liiological llatf-Lives for Radiopharmaceuticals Excreted in lircast Milk (Continued)
I
- Biological IIalf-Life Measured for Excretion Fractions
- Excretion Radiopharmaceutical a T. (5 -) -.5brarence Tc-99m DTPA 7.2E-7 (2.2) 15 M O84*
6.0E-7 (2.8) 15 M085 5.0E-496 - 2.4E-3ff 6.5-30 RU94
~5.0E-7 (~3) 9.6 AH85 Tc-99m DTPA Aerosol Praction of administered acrosol assumed to reach bloodstream (0.406) treated as Tc-99m DTPA.
Tc 99m Glucoheptonate 1.4E 3ff 9.0 RU94 2.6E-6 12 M O87 Tc-99m HAM 8.8E-366 - 1.1E-266 6.0-(7.0)tt RU94 Tc-99m MAA 1.4E-4 (2.2) 20 MOS4 7.1E-6 (5) 3.1E-4 (7) 5.2-45 MA81 2.4E-5 (4) 53 BE73 1.4E-4 (35) 12 " CR85 7.0E-6 (6) ~ 12 HE79 4.0E-365 - 5.2E-265 73-18 AH85 Tc-9)m MAG 3 Treated as Tc-99m DTPA (renal agent for which data exist).
Tc-99m MDP/HDP ~ 1.6E-6 (~ 4) 8.4-34 AH85 Tc-99m MIBl 1.4E-6 (33) 23 RU916 1.0E-4fl - 3.0E-4fl 18-(6.7)tt RU94
~6.7E-6 (8.5) RU78 Tc-99m 04 (Pertechnetate) 2.6E-5 (10) - 6.4E 5 (2) 9-66 WY73 1.4E-4 (22) 20 VA71
~13E-5 (3) Pl79 7.19E-3 (2.4) - 1.7E-2 (2) OG83t
~5.0E-4 (~5) 6.9 AH85 1.7E-4 (8.2) 6 MOS7 1.4E.4 (~3) 5.2 HE86 Tc-99m PYP 1.5E-365 4.4E-3}l 8.4-(6.8)tt RU94 Tc-99m RBC - 2.0E-466 - 3.0E-465 (7.8-9.0)t t RU94 j in Vitro Labeling l
l NUREG-1492 11.6
Table B.2 Excretion Fractions and Biological flatf Uves Lr Radiopharmaceuticals Excreted in Breast Milk (Continued)
- Biological llatf Life Measured for Excretion Fractions
- Excretion Radiopharmaceutical -. -. 7, (br) Reference Tc-99m RBC - 6.0E-356 - 1.0E-266 (7.7)tt R O90 . . - ,
In Vivo Labeling (6.8)tt R O90 i 4.5E-5 (8)
~ 1.0E-7 (~ 4) (7)tt AH85 Tc-99m Sulphur Colloid 1.6E-3fl 1.5E-2il 35-(8.3)tt RU94 Tc-99m White Blood Cells Treated as Tc-99m pertechnetate, as fraction of free Tc-99m is ,
highly variable. i TI 201 Chloride 2.2E-6 43 MU89 (2 com-1.9E-7 (362)tt pa-tment model) 1.7E-6 13 JO95 (2 com-9.5E-7 164 partment model)
Xe-133 Gas Insignificant Dose to the breast-feeding infant. 1 i
- Peak ftaction per milliliter of milk. All values corrected to the time of activity administration. The number in l parenthesis is the time (hr) at which this maximum was observed. If data from more than one patient are reported, l data are presented as a range. !
- Pooled data from 4 patients.
i t Patient admitted for study of enlarged thyroid.
$ Conservative value chosen due to anecdotal report (n=1) (see addendum of MOS4). l 5 Data in Table 1 of RU91 recalculated due to possible errors in derived values for the percent excreted in milk.
il Total fraction excreted - milk concentrations not given, it For some radiopharmacueticals, T, may be negative (i.e., values shown in parentheses) because these were the unusual cases reported in the literature in which the the effective half-life was greater than the radionuclide's i
l physical half-lift (i.e., T, > T, ir" -tin ~ d activity a,cumulation).
- Speciation tests indicated that the activity excreted was most hkely in the form of Nal, s mlBG.
l l
l IL7 NUREG-1492 j
l -
l l
Table B3 Biological and Physical Parameters Used to Calculate the Total Activty Ingested and Internal Rndiation Doses Received from the intake of Radiopharmaceuticals in Breast Milk
- Biological Italf-Life Excretion Fraction"' for Excretion
- Administered Activity Lowest flighest Shortest Longest Radiopharmaceutical (mCl), , _ a, a3 Tu (hr) Tu (hr) 0.05 3.2E-7 1.4E4 5 7 Cr-51 EDTA 5 8.0E-6 1.0E-4 20 390 Ga-67 Citrate 10 7.2E-6 7.2E-6 85 85 1-123 mlBG 2 2.9E-5 1.5E-4 4.8 10.2 1-123 OlH 0.4 6.2E-5 6.5E-5 10.4 10.4 1-123 Sodium Iodide (Nal) 0.01 7.1E-5 7.1E-5 4.8 4.8 1-125 0111 0.3 43E-5 1.2E-4 2.2 6.0 1-131 0111 150 1.4E-5 6.7E-4 7.6 117 1-131 Sodium lodide (Nal)
In-111 White Blood Cells 0.5 2.4E-7 7.3E-7 (85) (140) 8 3.4E-6 4.6E-6 10 (9.1)
Tc-99m DISIDA 20 5.0E-7 6.5E-6 6.5 30 Tc-99m DTPA 2.0E-7 2.7E-6 6.5 30 Tc-99m DTPA Aerosol 1 20 2.6E-6 4.9E-6 9 12 Tc-99m Glucoheptonate 8 1.8E-5 2.3E-5 6 (7)
Tc-99m IIAM 4 7.0E-6 3.1E-4 5.2 45 Tc-99m MAA 10 5.0E-7 6.5E-6 6.5 30 Tc-99m N.sG3 20 1.6E-6 1.6E-6 8.4 34 Tc-99m MDP 30 2.2E-7 1.4E-6 18 (6.7)
Tc-99m MIBI 30 6.7E-6 1.7E-4 5.2 66 Tc-99m 0. (Pertechnetate) 20 3.1E-6 9.2E-6 8.4 (6.8)
Tc-99m PYP Tc-99m RBC - In Vitro Labeling 20 3.3E-7 5.0E-7 (7.8) (9)
Tc-99m RBC - In Vivo Labeling 20 1.0E-7 4.5E-5 (6.8) (7) l l
l l
N U R EG-1492 II.8
Table 11.3 lliological and Physical Parameters Used to Calculate the Total Activty Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in lircast Milk (Contiuned) filological Ifalf Life Excretion Fraction m for Excretionm Administered Activity Lowest liighest Shortest Longest Radiopharmaceutical (mCl) as a2 T,i (br) T,2 (hr) 12 2.8E-6 2.6E-5 35 (8.3)
Tc-99m Sulfur Colloid 30 6.7E-6 1.7E-4 5.2 66 Tc-99m White Blood Cells 3 1.7E-6 2.2E 6 13 43 TI-201 Chloride 9.5E-7 1.9E-7 43 (362)
- " Lowest" and *Ilighest" in this table refer to the lowest and highest concentration observed at peak for a given radiopharmaceutical by any author (see Table B.2 for references). Dese are combined with the shortest and longest biological half-lives for that radiopharmaceutical reported by any author. A given concentration and half-hfe combined to produce a supposedly best case or worrt case scenario did not necessarily come from the same study.
- For some radiopharmacueticals, T., and/or T. may be negative (i.e., values '.aown in parentheses)because these were the unusual cases reported in the literature in which the the effective half-life was greater than the radionuchde's physical half-life (i.e. 7, > T, indicates continued activity accumulation).
In these cases, the effective half-life was used to perform the analysis. ;
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t 11.9 NU REG-1492
1 .
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l Table IIA Total Activity ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in Breast Milk Under Different interruption Schedules l l
Total Activity Effective Dose Equivalent * ) '
Administered Interruptx.>n (mrem)
Ingested Radu, n- Activity Time i Concentration (hr) (mci) (%) Newborn 1 Yr-Old pharmaceutical (mci)
" L.v5 minimum 3 7.71E-06 1.54E -02 8.85E-04 3.71E-04 Cr-51 ED1 A 12 3.14E-06 6.27E-03 3.60E-04 1.518 - 04
~~
24 9.44E-07 1.89E-03 1.08E-04 4.54E-05 48 8.55E -08 1.71E-04 9.81E-06 4.11E-06 96 "' .02 E - 10 1.40E-06 8.06E ? 3.38E-08 120 6.378 -11 1.27E-07 7.30E-09 3.06E-09 i 168 5.23 E-13 1.05E-09 6.00E-11 2.51E-11 l 336 1.56E-20 3.12E-17 1.798 -11 7.50E-19 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E +00 maxmimum 3 3.378 -05 6.75 E-02 3.87E-03 1.62E-03 12 1.37E-05 2.74E -02 1.57E-03 6.60E-04 24 4.13E-06 8.26E-03 4.74E-04 1.99E-04 48 3.74E-07 7.48E-04 4.29E-05 1.80E-05 96 3.07E-09 6.15E-06 3.53E-07 1.48E-07 120 2.79E-10 5.57E-07 3.198 -08 1.34E-08 168 2.29E- 12 4.58E-09 2.62E-10 1.10E-10 336 6.82E-20 1.36E-16 7.82E-18 3.28E- 18 672 0.00E +00 0.00E + 00 0.00E +00 0.00E +00 4.09E-02 8.17E-01 2.72E + 02 1.04E + 02 Ga-67 Citrate 5 minimum 3 12 2.76E-02 5.52E-01 1.84E + 02 7.05 E + 0!
24 1.64E-02 3.28E-01 1.098 + 02 4.18E + 01 48 5.77E-03 1.15E-01 3.84E + 01 1.47E +01 96 7.14E-04 1.43E-02 4.76E +00 1.82E +00 120 2.51E-04 5.03E-03 1.67E +00 6.42E-01
'68 3.! !E -05 6.23E-04 '. 07E -01 7.955 -02 336 2.08E-08 4.17E-07 1.39E-04 5.32E-05 672 9.27R-15 1.85E-13 6.17E-11 2.37E-11 1.99E + 00 3.98E + 01 1.33E +04 5.08E + 03 maxmimum 3 12 1.81E + 00 3.62E + 01 1.20E+04 4.62E +03 24 1.59E + 00 3.18E + 01 1.06E + 04 4.06E 4 03 48 1.23 E + 00 2.47E + 01 8.21E +03 3.15E +03 96 7.40E-01 1.48E + 01 4.93E+03 1.89E +03 120 5.73E-01 1.1553 +01 3.82E + 03 1.46E + 03 3.44E-01 6.88E + 00 2.29E + 03 8.7BE + 02 168 336 5.76E-02 1.15E + 00 3.83E + 02 1.47E +01 672 1.61E-03 3.23E-02 1.07E + 01 4.12E +00 l
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11.1 0 NURiiG.1492
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Table IIA Total Activity Ingested and laternal Radiation Doses Received from the intake of Radiopharmaceuticals in fireast Milk Under Dilierent Interruption Schedules (Continued)
- '^* I ** " " "'
Administered in:u. ption (m m )
In8estM Radio. Activity Time pharmaceutical (mci) Concentration (br) (mci) (%) Newborn 1-Yr-Old 1-12f rEldG* 10 minimum 3 5.41E-02 5.41E-01 3.20E + 02 2.20E + 02 12 3.13E-02 3.13E-01 1.86E + 02 1.28E + 02 24 1.51E-02 1.51E-01 8.978 +01 6.16E + 01 48 3.53E-03 3.53E-02 2.10B + 01 1.44E + 01 96 1.92E-04 1.92E-03 1.198 + 00 8.02E -01 120 4.48E-05 4.48E-04 3.04E-01 1.998 - 01 168 2.44E-06 2.44E-05 4.01 E--02 2.09E-02 336 9.15 E-11 9.15E-10 6.03E-03 2.57E-03 672 0.00E +00 0.00E + 00 3.31E-04 1.41E-04 .
maxmimum 3 5.41E-02 5.41E-01 3.20E + 02 2.20E +02 12 3.13 E-02 3.13R-01 1.E6E +02 1.28E + 02 24 1.51E-02 1.51E-01 8.97E +01 6.16E + 01 48 3.53E-03 3.53E-02 2.10E + 01 1.44E + 01 96 1.92E-04 1.92E-03 1.19E +00 8.02E-01 120 4.48E-05 4.4BE -04 3.04E-01 1.99E-01 168 2.44E-06 2.44E-05 4.01E-02 2.09E-02 336 9.15 E-Il 9.15 E-10 6.03 E-03 2.57E-03 672 0.00E +00 0.00E + 00 3.31E-04 1.41 E-04 minimum 3 1.63 E-02 8.13E-01 3.85 E +00 1.62E + 00 l-123 O1H* 2 12 2.76E -03 1.3&B-01 6.54E-01 2.76E-01 24 2.60E-04 1.30E-02 6.17E-02 2.60E-02 48 2.31E-06 1.15E-04 5.49E-04 2.32E-04 96 1.82E- 10 9.08E-09 4.46E-08 1.89E-08 120 1.61E-12 8.06E-11 4.32E-10 1.82E - 10 1 168 8.79E-17 4.40E-15 6.84E-14 2.88E-14 !
336 0.00E + 00 0.00E +00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00E +00 0.00E + 00 marmimum 3 1.24E-01 6.18E+ 00 2.93E+ 01 1.24E+ 01 I l
12 4.18E-02 2.09E + 00 9.92E + 00 4.18E + 00 24 9.86E-03 4.93E -01 2.33E +00 9.865E -01 f 48 5.48E-04 2.74E-02 1.31E-01 5.49E-02 l 96 1.69E-06 8,45E-05 4.19E-04 1.77E-04 l 120 9.38E-08 4.69E-06 2.59E-05 1.09E-05 168 2.89E-10 1.45 E -08 2.09E-07 8.78E-08 i 336 0.00E + 00 0.00E + 00 1.43E-12 6.00E -13 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 uummmmmmeemummmmmmmmer I
- Include the dose from radioactive contaminants. See Section B.1 CALCULATION AL METHOD for details.
i 11.1 1 NURiiG- 1492
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Table 11.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued)
Total Activity Effective Dose Equivalent Administered later. ; ion Time I" # ( *"
Radio- Activity Concentration (br) (mci) (%) Newborn I-Yr.Old pharmaceutical (mci) 0.4 minimum 3 1.03 E-02 2.58E 4 00 6.12E + 0! 4.21E + 01 .
l.123 Nal*
12 3.53E-03 8.83E-01 2.09E + 01 1.44E + 01
~
24 8.45E'-04 ' 2.11E-01 5.01E + 00 3.45E + 00 l 41 4.84E -05 1.21E-02 2.89E-01 1.988 -01 96 1.598 -07 3.98E-05 9.61E-04 6.62E-04 120 9.12E-09 2.28E-06 5.61E-05 3.86E-05 168 3.00E-11 7.49E-09 2.02E-07 1.40E-07 336 0.00E + 00 0.00E + 00 5.08E-15 3.68E-15 672 0.00B + 00 0.00E +00 0.00E + 00 0.00E +00 i 1.08E-02 2.70E + 00 7.04E + 01 4.87E + 01 l maxmimum 3 12 3.70E-03 9.25E-01 2.83 E + 01 1.98E +01 !
24 8.86E-04 2.22E-01 1.17E + 01 8.27E +00 t 48 5.08E-05 1.27E-02 6.74E +00 4.87B + 00 96 167E-07 d.17E-05 6.44E + 00 4.66E + 00 120 9.56E-09 2.39E-06 6.44E + 00 4.66E + 00 l 168 3.14E- 11 7.85E-09 6.44E +00 4.668 +00 336 0.00E + 00 0.00E + 00 6.44E + 00 4.66E + 00 672 0.00E + 00 0.00E + 00 7.82E-01 5.66E-01 0.01 minimum 3 2.52E -04 2.52E + 00 2.24E-01 9.04E-02 1125 O!H 12 6.84E-05 6.848 -01 6.07E-02 2.45 E-02 24 1.20E-05 1.20E-01 1.07E-02 4.31E-03 48 3. 2E-07 3.72E-03 3.30E-04 1.33E-04 96 3.55E -10 3.55E-06 3.15 E-07 1.27E-07 120 1.10E-11 1.10E-07 9.75E-09 3.94E- 09 ,
3.778 - 12 l 16s 1.05 E- 14 1.05 E-10 9.32E -12 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E +00 1 672 0.00E + 00 0.00E + 00 0.00E +00 0.00E + 00 maxmimum 3 2.52E-04 2.52E + 00 2.24E-01 9.04E-02 12 6.84E-05 6.84E-01 6.07E-02 2.54E-02 24 1.20E -05 1.20E-01 1.07E -02 4.31E-03 48 3.72E-07 3.72E-03 3.30E-04 1.33E-04 96 3.55 E- 10 3.55E-06 3.15 E-07 1.27E-07 120 1.10E-11 1.10E-07 9.75 E-09 3.94E-09 168 1.05 E- 14 1.05 E- 10 9.32E-12 3.77E-12 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00
- Includes the dosc from radioactive contaminants. See Section B.1 CALCULATIONAL METHOD for details.
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NU R EG.1492 11.1 2
l Table 11.4 Total Activity ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in lircast Milk Under Different interruption Schedules (Continued) otal AcGity Mccdu Nse uguhalent Administered interruption ,ntum)
In W ed .
Radio- Activity Time (hr) (mCD (%) Newborr. 1-Yr-Old pharmaceutical (mCD Concentration 3 2.62E-03 8.73E-01 2.91F i 00 1.16E + 00 1-13i OIH 0.3 minimum 12 1.498 - 04 4.96E-02 1 MB-01 6.61E-02 24 3.26E-06 1.09E-03 3.61E-03 1.45E-03 48 1.36E-09 5.19E-07 1.73E-06 6.91E-07 96 3.48E-16 1.16E-13 3.86E-13 1.54E-13 120 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 168 0.00E +00 0.00E + 00 0.00B + 00 0.00E + 00 336 0.00E + 00 0.00B + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E +00 1.50E-02 4.99E + 00 1.668 +01 6.65E + 00 maxmimum 3 12 5.13E-03 1.71E + 00 5.69E + 00 2.29E + 00 24 1.23 E-03 4.09B-01 1.36E + 00 5.45E-01 48 7.05E-05 2.35E-02 7.82E-02 3.13E-02 96 2.32E-07 7.73E-05 2.58E-04 1.03 E-04 120 1.33E-08 4.44E-06 1.48E-05 5.91E-06 168 4.38E-11 1.46E-08 4.86E-08 1.95E-08 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00B +00 0.00E +00 minimum 3 1.06E + 00 7.07E-01 2.08E + 07* 1.53E + 07*
F131 Sodiu.n Iodide 150 12 4.52E-01 3.01E-01 8.86E + 06* 6.52E + 06*
(Nal) 2.09E + 06*
24 1.45E-01 9.66E-02 2.84E + 06*
48 1.49E-02 9.94E-03 2.92E + 05
- 2.15E + 05*
96 1.58E-04 1.05E-04 3.10E + 03
- 2.28E + 03
- l 120 1.62E-05 1.08E-05 3.18E + 02
- 2.33 E + 02*
168 1.71E-07 1.14E-07 3.35E + 00* 2.47E + 00*
336 1.92E-14 1.28E-14 3.76E -07
- 2.77E-07*
672 0.00E + 00 0.00E +00 0.00E + 00* 0.00E +00* l maxmimum** 3 7.50E+ 01 5.00E + 01 1.47E + 09
- 1.08E + 09' j 12 7.50E + 01 5.00E + 01 1.47E + 09
- 1.0SE + 09*
24 7.50E + 01 5.00E + 01 1.47E + 09
- 1.08E + 09*
48 7.50E + 01 5.00E + 01 1.47E + 09
- 1.08E + 09*
96 7.50E + 01 5.00E + 01 1.47E + 09* 1.08E + 09*
l 120 7.50E +01 5.00E + 01 1.47 E + 09
- 1.08E + 09
- 168 7.50E + 01 5.00E + 01 1.47E + 09* 1.0BE4 09*
336 1.88E + 01 1.25E + 01 3.69 E + 08
- 2.71 E + 08
- 672 7.68E-01 5.12E-01 1.51E + 07
- 1.11E + 07*
- Dose to the infant thyroid, mrad.
- The values under Total Activity Ingested and Effective Dose Equivalent for intenuption times 3 to 168 hours0.00194 days <br />0.0467 hours <br />2.777778e-4 weeks <br />6.3924e-5 months <br /> show no change with time because the total fraction of administered activity excreted in the breast milk exceeded the upper limit (or cap) of 0.50 (see Section B.1 C ALCULAT10N AL METHOD).
l l
I 11.1 3 NU REG.1492
Table 11.4 Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued) otal ActMy NGe hse Qukatent Administered Interruption lagsted (narent)
Radio- Activity Time i
(hr) (mci) (%) Newborn I-Yr-Old pharmaceutical (mci) Concentration 3 6.21E-04 1.24E-01 3.53E + 01 1.32E + 01 In-!!! 0.5 minimum 5.77B-04 1.15 E-01 3.29E + 01 1.23E + 01, _
12 White BhiodCells* 1.11E + 01 24 5.23E-04 1.05 E-01 2.98E + 01 48 4.30E-04 8.608 - 02 2.45E + 01 9.15E + 00 96 2.91E-04 5.82E-02 1.66E + 01 6.19E +00 120 2.39E-04 4.78E-02 1.368 + 01 5.09E +00
[ 168 1.62B-04 3.23E-02 9.21E +00 3.44E +00 336 4.11E-05 8.22E-03 2.34E +00 8.74E-01 672 2.66E-06 5.318 - 04 1.51E-01 5.65E-02 3.10E-f,3 6.19E-01 1.76E + 02 6.59E + 01 maxmimum 3 2.96E- 03 5.92F -01 1.69E + 02 6.29E + 01 12 l 5.58E-01 1.59E +02 5.93E + 01 24 2.79E-03 l 4.95E-01 1.41E + 02 5.27E + 01 48 2.48E-03 96 1.95 E-03 3.91 E-01 1.11 E + 02 4.16E +01 1.73E-03 3.47E-01 9.88E + 01 3.69E +01 120 1.37E-03 2.74E-01 7.79E + 01 2.91E + 01 168 5.95E-04 1.19E-01 3.39E +01 1.27E + 01 336 672 1.13E-04 2.26E-02 6.43E+00 2.40E+ 00 5.64E-03 9.?9E-02 6.80E + 00 3.25 E + 00 Tc-99m DISIDA B minimum 3 12 1.07E-03 1.90E-02 1.29E + 00 6.18E-01 24 1.17E-04 2.07E-03 1.41E-01 6.74E-02 48 1.39E -06 2.47E-05 1.6BE-03 8.03E-04 96 1.97E-10 3.50E-09 2.38E-07 1.14E-07 120 2.35 E-12 4.16E-11 2.83E-09 1.36E-09 168 3.21 E-16 5.69E-15 3.87E-13 1.85E-13 0.00E +00 0.00E +00 0.00E +00 0.00E + 00 336 0.00E + 00 0.00E + 00 0.00E+ 00 0.00E + 00 672 2.25E-02 2.82E-01 1.92E + 01 9.17E + 00 maxmimum 3 1.13 E-02 1.42E-01 9.66E + 00 4.62E + 00 12 4.55E-03 5.69E-02 3.87E + 00 1.85 E + 00 24 48 7.32E-04 9.15E-03 6.23 E-01 2.98E -01 96 1.89E -05 2.36E-04 1.61E-02 7.70E-03 120 3.04E -06 3.80E-05 2.59E-03 1.24E-03 168 7.86E-08 9.83E-07 6.69E-05 3.20E-05 336 2.18E-13 2.73E -12 1.86E-10 8.89E-11 0.00E + 00 0.00E + 00 0.00E+ 00 0.00E + 00 672 ammmmmmmt
- Includes the dose from radioactive contaminants. See Section B.1 CALCULATIONAL METHOD for details.
H,14 NU REG-1492 -
l Table II.4 Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmac,euticals in Ilreast Milk Under Different Interruption Schedules (Continued) o al AcMty Nee Nse Quhalent Administered Interruption "*'
I"E'S**d Rad'w Activity Time (mci) (%) Newborn I-Yr-Old pharmaceutical (mci) Concentration (hr) 2.57B-03 1.29E-02 3.23 E-01 1.43E -01 m Tc-99m DTPA 20 minimum 3 12 3.49E-04 1.74E-03, , 4.39E-02 1.94E-02 24 2.43B-05 1.22E-04 3.06E-03 1.35B-03 48 1.18E-07 5.92E-07 1.49E-05 6.57E-06 96 2.80E -12 1.40E-11 3.52E-10 1.55E-10 120 1.36E-14 6.80E-14 1.718 -12 7.55 E- 13 168 0.00E + 00 0.00E + 00 0.00E +00 0.00E + 00 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E+ 00 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 3 4.78E-02 2.39E-01 6.02E + 00 2.65E + 00 maxmimum 12 1.38E-02 6.88E-02 1.73E +00 7.64E-01 24 2.61 E-03 1.3 tE-02 3.29E -01 1.45E-01 48 9.43E-05 4.72E-04 1.19E-02 5.24E-03 96 1.23E-07 6.14E-07 1.55E-05 6.82E-06 120 4.43 E-09 2.22E-08 5.58E-07 2.46E-07 168 5.77E-12 2.89E- 11 7.26E -10 3.23 E-10 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E +00 672 0.00E + 00 0.00E + 00 0.00E +00 0.00E +00 3 5.14E-05 5.14E-03 1.43E-02 6.09 8 - 03 Tc-99m DTPA 1 minimum 12 6.98E-06 6.93E-04 1.94E-03 8.26E-04 Aerosol 24 4.87E-07 4.878 - 05 1.35 E-04 5.76E-05 48 2.37E-09 2.37E-07 6.57E-07 2.80E-07 96 5.60E-14 5.60E-12 1.55E-11 6.63E-12 120 2.72E-16 2.72E- 14 7.55 E-14 3.22E-14 168 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 336 0.00E +00 0.00E + 00 0.00E + 00 0.00E +00 672 0.00E + 00 0.00E + 00 0.00E +00 0.00E 400 3 9.93E-04 9.93E-02 2.76E-01 1.18E-01 maxmimum 12 2.86E-04 2.86B-03 7.93E-02 3.38E-02 24 5.43E -05 5.43 E-03 1.51E-02 6.43E-03 48 1.96E-06 1.96E-04 5.44E-04 2.32E-04 96 2.55E-09 2.55E-07 7.08E-07 3.02E-07 120 9.21E-Il 9.21E -09 2.56E-08 1.09E-08 168 1.20E- 13 1.20E- 11 3.33E-11 1.42E-11 0.00E + 00 0.00E +00 0.00E + 00 0.00E + 00 336 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 11.1 5 N U R!iG- 1492
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Table 11.4 Total Activity ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued)
^* 'I
- ' * " "'*"I Administered Interruption (mrem)
Ingstd Radio- Activity Time (hr) (mci) (%) Newborn 1-Yr-Old pharmaceutical (mci) Concentration 3 1.48E-02 7.41E-02 5.38E + 00 2.30E +00 Tc-99m 20 minimum 12 2.63 E-03 1.31E-02 9.52E-01 4.088 - 01 Glucoheptonate 24 2.618 - 04 1.31B-03 9.48E-02 4.06B-02 48 2.59E-06 1.29E-05 9.38E-04 4.02E-04 96 2.53E-10 1.27E-09 9.19E-08 3.94E-08 120 2.51E- 12 1.25 8 - 11 9.10E-10 3.90E-10 168 2.21E-16 1.11E-15 8.03E-14 3.448 -14 336 0.00E + 00 0.00B + 00 0.00E + 00 0.00E +00 672 0.00E +00 0.00E + 00 0.00E +00 0.00B +00 3.02E-02 1.518 -01 1.10E +01 4.70E + 00 maxmimum 3 12 6.378 -03 3.19E-02 2.31E +00 9.90E-01 24 7.99E-04 3.99E-03 2.90E-01 1.248 -01 ,
48 1.25E-05 6.27E-05 4.55E-03 1.95B-03 l 96 3.10E-09 1.55 E-08 1.12E-06 4.81E-07 120 4.87E-11 2.43E-10 1.76E.-08 7.56E-09 168 1.19E- 14 5.97E-14 4.33E-12 1.86E-12 i
336 0.00E + 00 0.00B + 00 0.00E + 00 0.00B +00 0.00E + 00 0.00E +00 )
672 0.00E 4 00 0.00E + 00 l
3 3.60E-02 4.50E-01 2.00E+ 01 8.13E +00 Tc-99m ilAM B minimum 4.51 E-03 5.64E-02 2.50E + 00 1.02E +00 l 12 24 2.83E-04 3.54E-03 1.57E-01 6.38E-02 l 48 1.11 E-06 1.39B-05 6.17E-04 2.51B-04 96 1.72E-11 2.14E-10 9.52E-09 3.87E-09 120 6.73E- 14 8.42E-13 3.74E-11 1.52E- 11 )
168 0.00E + 00 0.00E +00 0.00E + 00 0.00E + 00 f 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E +00 (
672 0.00E + 00 0.00E + 00 0.00E +00 0.00E +00 (
3 8.95E-02 1.12E + 00 4.97E + 01 2.02E + 01 maxmimum 12 3.67E-02 4.59E-01 2.04E + 01 8.29E + 00 24 1.12E-02 1.40E-01 6.21E4 00 2.53E + 00 48 1.04E-03 1.30E-02 5.77E-01 2.35E-01 96 8,98E-06 1.12E-04 4.98E-03 2.03E-03 120 8.35E-07 1.04E-05 4.63E-04 1.88E-04 168 7.21E-09 9.01E-08 4.00E -06 1.63 E-06 336 3.00E- 16 3.75E - 15 1.66E- 13 6.76E-14 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 NU R EG-1492 H.16
Table 11.4 Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in lircast Milk Under Different Interruption Schedules (Continued)
Total Acdyhy EUecdve Nse Equivalent Interruption Administered Activity Time ' "#* ("'**
Radio-pharmaceutical (mci) Concentration (hr) (MCI) (%) Newborn 1-Yr-Old 4 minimum 3 6.66E-03 1.66E-01 4.19E + 00 1.70E + 00 Tc-99m M AA , .
12 7.11E-04 1.78E-02 4.47E-01 1.81E-01 l 24 3.60E-05 9.00E-04 2.26E-02 9.19E-03 !
48 9.23 E-08 2.31E-06 5.81E-05 2.36E-05 96 6.07E- 13 1.52E-11 3.82E-10 1.55E-10 ;
120 1.54E- 15 3.85E-14 9.698 - 13 3.93E-13 168 0.00E +00 0.00E + 00 0.00E + 00 0.00E +00 336 0.00E +C 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00E +00 0.00E + 00 maxmimum 3 4.78E-01 1.19E +01 3.01E + 02 1.22E +02 12 1.47E-01 3.68E + 01 9.27B + 01 3.76E +01 1 24 3.07E-02 7.68E-01 i.93E + 01 7.84E + 00 48 1.33 E-03 3.33E-02 8.38E-01 3.40E-01 96 2.51E -06 6.28E-05 1.58E-03 6.41E-04 120 1.09E-07 2.73B-06 6.86E-05 2.7FE-05 l 1.29E-07 5.25E-08 I 168 2.06E- 10 5.14E-09 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 1 672 0.00E + 00 0.00E +00 0.00E + 00 0.00E+ 00 l Tc-99m MAG 3 10 mimmum 3 1.29E-03 1.29E-02 1.52E-01 6.66E-02 12 1.74E-04 1.74E-03 2.07E-02 9.04E-03 24 1.22E-05 1.22E-04 1.44E-03 6.30E-04 48 5.92E-08 5.92E-07 7.00E- 06 3.06E-06 96 1.40E- 12 1.40E-11 1.66E-10 7.25E-11 120 6.80E - 15 6.80E-14 8.05E-13 3.528 - 13 163 0.00E + 00 0.00E + 00 0.00B + 00 0.00E + 00 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 0A '100E + 00 0.00E + 00 0.00E + 00 maxmimum 3 2.39 E-02 2.39E-01 2.83E + 00 1.24B + 00 12 6.88E-03 6.88E-02 8.15E-01 3.56E-01 24 1.31E-03 1.31E-02 1.55 E-01 6.77E-02 48 4.72E-05 4.72E-04 5.58E-03 2.44E-03 96 6.14E-08 6.14E-07 7.27E-06 3.18E-06 120 2.22E -09 2.22E-08 2.62E-07 1.15E-07 168 2.89E - 12 2.89E-11 3.42E-10 1.50E-10 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 B.17 N U R EG- 1492
Table 11.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Ilreast Milk Under Different laterruption Schedules (Continued)
Interruption To c y Edve se uhalent Administered Rad,o-i Activity Time Concentration (hr) (mCD (%) Newborn 1-Yr-Old pharmaceutical (mci)
To-99m MDP 20 minimum 3 8.94E-03 4.478 - 02 3.64E + 00 4 >1.?T ma . . _
12 1.51 E-03 7.53 E-03 6.13E-01 2.34E-01 24 1.40E-04 7.028 - 04 5.71E-02 2.18E-02 48 1.22E-06 6.09E-06 4.95 B-04 1.89E-04 96 1.16E-11 4.58E-10 3.73E-08 1.42E-08 120 7.94E-13 3.97E-12 3.238 -10 1.23 E-10 168 4.15E-17 2.08E-16 1.69E-14 6.45 8 - 15 336 0.00E + 00 0.00B +00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00B + 00 0.00E + 00 maxmimum 3 1.20E-02 5.988 -02 4.87E +00 1.86E + 00 12 3.53E-03 1.76B-02 1.44E + 00 5.48E-01 24 6.92E-04 3.46E-03 2.82E-01 1.08E-01 48 2.67E-05 1.33B-04 1.09E-02 4.14E-03 96 3.96E-08 1.98E-07 1.61E-05 6.15E-06 120 1.52E-09 7.62E-09 6.20E-07 2.37E-07 168 2.26E-12 1.13E-11 9.20E- 10 3.51E-10 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E +00 0.00E +00 0.00E +00 30 minimum 3 2.23E-03 7.44E-03 1.16E + 00 5.37E-01 Tc-99m MIBI 12 5.598 - 04 1.86E-03 2.90E-01 1.34E-01 24 8.83E-05 2.94E-04 4.57E-02 2.12E-02 48 2.20E-06 7.34E-06 1.14E-03 5.30E-04 96 1.37E-09 4.56E-09 7.09E-07 3.29E-07 120 3.41E-11 1.14E-10 1.77E-08 8.21E-09 l
' 58 2.12E -14 7.08E-14 .10E- 11 5.11E-12 l 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00E 400 0.00E + 00 3 1.97E-02 6.56E-02 1.02E +01 4.73E + 00 1 maxmimum 12 7.76E-03 2.59E-02 4.02E + 00 1.87B + 00 24 2.24E-03 7.47E-03 1.16E + 00 5.39E-01 48 1.87E-04 6.24E-04 9.70E-02 4.51E-02 96 1.31E-06 4.36E-06 6.77E-04 3.14E-04 120 1.09E-07 3.64E-07 5.66E -05 2.63E-05 168 7.62E-10 2.54E-09 3.95E-07 1.83E -07 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E+ 00 0.00E + 00 0.00E +00 I
I I
I NUREG-1492 H.18
Table 11.4 Total Activity Ingested and Internal Radiation Doses Received from the lutake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued) j Interruption otal ActMty Nve Nse Quivalent Administered Time I"A' I*'**)
Radio. Activity ,
i Concentration (hr) (mci) (%) Newborn 1-Yr-Old pharmaceutical (mCl) 30 mimmum 3 4.78E-02 1.59E-01 "i .^ 5 r M - - ; .02E + 00 Tc-99m 04 12 5.108 - 03 1.70E-02 2.08E + 00 9.63 E-01 (Pertechnetate) 24 2.58E-04 8.61E-04 1.05E-01 4.88E-02 48 6.63E-07 2.21E-06 2.70E-04 1.25E-04 j 96 4.36E- 12 1.45E-11 1.77E-09 8.23E-10 J 120 1.11E - 14 3.69E-14 4.50E-12 2.098 - 12 l 168 0.00E + 00 0.00E + 00 0.00E +00 0.00E +00 336 0.00E + 00 0.00E + 00 0.00E +00 0.00E +00 l 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E +00 maxmimum 3 2.03 E + 00 6.76E + 00 8.25E +02 3.83E + 02 2.66E +02 1.23E +02 l 12 6.54E-01 2.18E A00 24 1.44E-01 4.81 E-01 5.88E + 01 2.73E +01 )
48 7.05E-03 2.35 E-02 2.87E + 00 1.33E + 00 l 6.84E-03 3.17E-03 j 96 1.68E-05 5.61E-05 120 8.21E-07 2.74E-06 3.34E-04 1.55E-04 163 1.96E -09 6.53E-09 7.97E-07 3.69E-07 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E 4 00 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 minimum 3 1.73E-02 8.66E-02 4.81E+00 2.05E +00 Tc-99m PYP 20 12 2.92E-03 1.46E-02 8.10E-01 3.46E-01 24 2.72E-04 1.36E-03 7.55E-02 3.22E-02 48 2.36E -06 1.18E-05 6.54E-04 2.79E-04 96 1.77E - 10 8.87E-10 4.92E-08 2.10E-08 j 120 1.54E-12 7.70E-12 4.27E-10 1.82E-10 168 8.05 E-17 4.02E-16 2.23E-14 9.53E-15 336 0.00E + 00 0.00E +00 0.00E +00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00E +00 0.00E + 00 maxmimum 3 8.73E -02 4.37E-01 2.42E + 01 1.03E +01 12 3.49E-02 1.74E-01 9.68E + 00 4.13E + 00 24 1.03E-02 5.14E -02 2.85E + 00 1.22E + 00 48 8.90E-04 4.45 E -03 2.47E-01 1.05E-01 96 6.68E-06 3.34E-05 1.85E-03 7.91E-04 120 5.79E-07 2.90E-06 1.61E-04 6.86E-05 168 4.35E-09 2.17E-08 1.21E-06 5.15E-07 336 4.20E- 17 2.10E-16 1.17E-14 4.97E -15 672 0,00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 mummmmmmmmmmenemum mmmmmmmmmmmmmmer i
i 1119 NURE(i-1492
I s
Table H.4 Total Activity ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in Hreast Milk Under DitTerent Interruption Schedules (Continued)
Total Aedvity Mecdve hse 4uivalent Administered Intes. . ion ("*##"I l
Time I"E"I Radio- Active =
Concentration (hr) (mci) (%) Newborn 1-Yr.Old pharmaceutical (mci) 20 minimum 3- 3.53E-03
- 7C -G
. ' t.10E + 00 4.83 E-01 ,
Tc-99m RBC l 12 1.58E-03 7.928 -03 4.93E-01 2.17E -01 in Vitro Labeling . , , ,
24 5.46E-04 2.73 B-03 1.70E-01 7.47E-02 l 48 6.47E -05 3.24E-04 2.01E-02 8.86E-03 96 9.10E-07 4.55E-06 2.83E-04 1.25E-04 i 120 1.08E-07 5.398 -07 3.35E-05 1.48E-05 168 1.52E-09 7.58E-09 4.71E-07 2.08E-07 I
336 4.95 E-16 2.48E-15 1.54E-13 6.78E-14 672 0.00E +00 0.00E + 00 0.00E + 00 0.00E + 00 3 6.06E-03 3.03E-02 1.88E + 00 8.30E-01 j maxmimum 12 3.03E-03 1.52E-02 9.42E-01 4.15 E-01 3.74E-01 1.65E-01 i 24 1.20E -03 6.01E-01 48 1.90E-04 9.48E-04 5.o9E-02 2.59E-02 ,
96 4.70E-06 2.35E-05 1.46E-03 6.44E-04 120 7.41 F -7, 3.71E-06 2.30E-04 1.01 E-04 168 1.84E-08 9.20E-08 5.728 - 06 2.52E-06 336 4.43E-14 2.22E-13 1.3BE- 11 6.07E-12 672 0.00E + 00 0.00E + 00 0.00E +00 0.00E + 00 20 minimum 3 9.49E-04 4.75 E-03 2.88E-01 1.30E-01 Te-99m RBC 12 3.79E-04 1.90E-03 1.15E-01 5.19E-02 In Vivo Labeling 24 1.12E-04 5.5BE-04 3.39E-02 1.53E-02 48 9.67E-06 4.84E-05 2.94E-03 1.328 -03 96 7.26E-08 3.6J E-07 2.20E-05 9.94E-06 120 6.29E-09 3.15 E-08 1.91E -06 8.62E-07 l 16e 4.73E-11 2.36E-10 1.43E-OS 6.47E-09 )'
336 4.57E-19 2.28E-18 1.39E-16 6.2SE-17 672 0.00E +00 0.00E + 00 0.00E + 00 0.00E + 00 3 4.38E-01 2.19E + 00 1.33 E +02 5.99E + 01 maxmimum 12 1.80E-01 8.98E-01 5.45E + 01 2.46E + 01 24 5.4BE-02 2.74E-01 1.66B + 01 7.50E + 00 48 5.09E-03 2.54E-02 1.54E + 00 6.96E-01 96 4.39E-05 2.20E-04 1.33E-02 6.01E-03 120 4.08E -06 2.04E-05 1.24E-03 5.59E-04 168 3.52E-08 1.76E-07 1.07E -05 4.82E-06 336 1.47E-15 7.33E -15 4.45 E -13 2.01 E-13 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 i
i
[
l NU R EG-1492 IL20
l l
1 Table II.4 Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in lircast Milk Under Different Interruption Schedules (Continued) oalAc ty ve se u alent Administered Interruption Radio- Activity Time
- ("*I pharmaceutical (mci) Concentration (br) (mci) (%) Newborn 1-Yr-Old Tc-99m 12 minimum ~ ~J 4.20E -02 1.05E-01 9.33E + 00 4.57E + 00 -
Sulfur Colloid 12 3.74E-03 3.11E-02 2.76E + 00 1.35B +00 24 7.38E -04 6.15 E-03 5.46E -01 2.68E-01 48 2.88E-05 2.40E-04 2.13E-02 1.05E-02 96 4.40E-08 3.67E-07 3.262 -05 1.60E-05 120 1.72E-09 1.43E-08 1.27E-06 6.23E-07 168 2.628 - 12 2.19E -Il 1.94E-09 9.51E-10 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E +00 672 0.00E +00 0.00E +00 0.00E + 00 0.00E+ 00 maxmimum 3 1.76E-01 1.47E + 00 1.30E + 02 6.38E+ 01 12 8.30E-02 6.92E-01 6.14E + 01 3.01E +01 24 3.05E-02 2.54E-01 2.26E +01 1.11E + 01 48 4.11E-03 3.42E -02 3.04E + 00 1.49E + 00 96 7.47E-05 6.22E-04 5.53 E-02 2 71E-02 120 1.01 E-05 8.39E-05 7.45E-03 3.65E-03 168 1.83 E -07 1.53 E -06 1.35E-04 6.64E-05 336 1.48E-13 1.23E - 12 1.09E- 10 5.36E-11 672 0.00E + 00 0.00E +00 0.00E + 02 0.00E +00 30 minimum 3 4.78E-02 1.59B-01 1.95E +01 9.02E + 00 Tc-99m White EkaxlCdis* 12 5.10E-03 1.70E-02 2.08E +00 9.63E -01 24 2.58E-04 8.61E-04 1.0$E-01 4.88E-02 48 6.63E-07 2.21E-06 2.70E-04 1.25E-04 96 4.36E-12 1.45 E-11 1.77E-09 8.23E-10 120 1.11E-14 3.69E -14 4.50E-12 2.09E-12 168 0.00E + 00 0.00E + 00 0.00E +00 0.00E + 00 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 maxmimum 3 2.03E + 00 6.76E + 00 8.25 E + 02 3.83E + 02 12 6.54E-01 2.18E + 00 2.66E + 02 1.23E+ 02 24 1.44E -01 4.81E-01 5.88E + 01 2.73E + 01 48 7.05E-03 2.35E-02 2.87E + 00 1.33E + 00 96 1.68E-05 5.61 E -05 6.84E-03 3.17E-03 120 8.21 E -O' 2.74E -06 3.34E -04 1.55E-04 168 1.96E-J9 6.53 E -09 7.97E-07 3.698 -07 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E -00 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00
- 7he dose estimates for Te-99m labeled white blood cells are actually the dose estimms for Tc-99m penechnetate, as it was assumed that activity released in breast milk from this product would be in the form of pertechnetate.
l l
l l
l l
11.2 1 NUREG-1492 l
j .
l Table 11.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Ilreast Milk Under Different Interruption Schedules (Continued)
- '^* *** "
- N" ' #"I Administered Interruption Radio- Activity Time ' "E" ' (*#'"
pharmaceutical (mci) Concentration (hr) (mci) (%) Newborn 1-Yr-Old TI-201 Chloride
- 3 muwndo- 3 1.22E-02 4.08E-01 1.94E +02 1.11E + 02 12 9.72B-03 3.24E-01 1.54E +02 8.78E +01 24 7.49E-03 2.50E:01 1.18E +02 6.74E + 01 ,
48 4.92E-03 1.64E-01 ', .73E + 01 4.42E + 01 l 96 2.45E-03 8.17E-02 3.84E +01 2.19E + 01 120 1.76E-03 5.86E-02 2.76E + 01 1.57E + 01 168 9.10E-04 3.03 E-02 1.43E + 01 8.15E +00 336 9.11E-05 3.04E-03 1.43E+00 8.15E-01 672 9.13E-07 3.04E-05 1.43E-02 8.17E-03 2.37E-02 7.91E-01 3.67E + 02 2.10E +02 l maxmimum 3 12 2.12E-02 7.08E-01 3.29E + 02 1.87E + 02 l 24 1.86E-02 6.21E-01 2.88E + 02 1.65E + 02 48 1.51E -02 5.04E-01 2.34E + 02 1.34E +02 96 1.16E-02 3.88E-01 1.80E +02 1.03E +02 120 1.07E-02 3.56E-01 1.65E + 02 9.43 E + 01 168 9.41E-03 3.14E-01 1.45E + 02 8.31 E + 01 336 6.71E -03 2.24E-01 1.04E + 02 5.93E + 01 672 3.53E -03 1.18E-01 5.45E + 01 3.11E + 01
- Includes the dose from radioactive contaminants. See Section B.1 CALCULATIONAL METHOD for details.
NURIIG 1492 11.2 2
o I
Table H.S Potential Doses to Breast Feeding Infants from Radiopharmaceuticals Administered :o a Woman if No Interruption of Ilreast-Feeding and Recommendations on Interruption of Ilreast Feeding ,
Internal Dose to Exte.nal Dose to Maximum Infant if No Infant if No Administered Interruption of Interruption of Recommendation i Radio- Activity' Breast-Feeding8 Breast-Feeding8 Instructions on Interruption of I
~
pharmaceutical (mci)"(6115q) (mrem) (mrem) Required?' Breast-Feeding' Cr-51 EDTA 0.05 (1.85) <0.01 2 no None Ga-67 Citrate 5 (185) 300-10,000 200 yes Interruption for about I month I-123 m!BG' 10 (370) 300 100 yes laterruption for about 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> I-123 Oll!' 2 04) 4-30 30 no None 1-123 Sodiem 0.4 (14.8) 60-70 5 no None lodide (Na!)
I I-125 0111' O.01 (0.37) 0.2 10 no None I-131 Oll!' O.3 (11.1) 3-20 70 no Nonc l-131 Sodium 150 (5,550) very large N A' yes Complete cessation is necessary to Iodide (Nal) avoid thyroid ablation in the infant In-111 0.5 (18.5)40-200 60 yes Interrupt 2on for White Blood Cells about I week Tc-99m DISIDA B (300) 7-20 20 no None Tc-99m DTPA 20 (740) 50 no None Tc-99m DTPA 1 (37) 0.01-0.3 3 no None Aerosol' Tc-99m 20 (740) 5-10 50 no None Glucoheptonate Tc-99m H AM 8 (300) 20-50 20 no None Tc-99m M AA 4 (148) 4-300 10 yes Interruption for about 12 hours1.388889e-4 days <br />0.00333 hours <br />1.984127e-5 weeks <br />4.566e-6 months <br /> Tc-99m M AG3' 0.2-3 30 no None 10 (370)
Tc-99m MDP 4-5 50 no None 20 (740)
Te-99m MIDI 30 (1,110) 1 10 80 no None Tc-99m 04 30 (1,110)20-800 80 yes interruption for about 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> (Pertechnetate)
Tc-99m PYP 5-20 50 no None 20 (740) 11.2 3 NU R EG-1492
s
- l i
e 1
Table 11.5 Potential Doses to lircast Feeding infants from Radiopharmaceuticals Administered to a l Woman if No Interruption of lircast Freding and Recommendations on Interruption of Ilreast Feeding (Continued) l
\
Internal Dose to External Dose to ,
Maximum infant if No Infant if No l Administered Interruption of Interruptiun of Recommendation l
. Radio- _
Activity' Breast-Feeding8 Breast-Feeding8 Instructions on Interruption of l pharmaceutical (mci) (MBq) (mrem) (mrem) Required 7 8 Breast-Feeding8 l Tc-99m RBC 20 040) 1-2 50 no None -
In Vitro Labeling Tc-99m RBC 20 040) 0.3 100 50 yes Interruption for in Vivo Labeling about 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br /> l l
Tc-99m 12 (444) 9 100 30 yes Interruption for Sulfur Colloid about 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br /> To-99m 5 (185)20-800 10 yes Interniption for White BhulCells" about 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> TI 201 Chloride 3 (111) 200-400 60 yes Interniption for :
about 2 weeks I I
1, Maximum activity normally administered.
- 2. Doses were calculated using the maximum administered activities shown in column 2. If smaller activities were to be administered, the doses would be proportionally smaller. %e doses were calculated for newborn infants; doses to one-year-old infants would be less than half the doses shown. If a dose range is shown, the range is due to individual variability and measu.ement variability as indicated by different measurements of concentrations in breast milk as shown in Table B.2. All values have been rounded to one significant figure. De external dose, typically small relative to the internal dose, is con:idered separatley ender column 4.
- 3. Dose to the infant from external radiation only during breast-feeding assuming no interruption of breast-feeding. Doses were calculated using an occupancy factor of 0.16 and an effective distance from source to receptor tissue of 0.2 meter. All values have been rounded to one significant figure. l
- 4. De decision on whether instructions are required by 10 CFR 35.75 is based on the sum of the maximum value of the internal dose range for the newborn infant plus the external dose assuming no interniption of breast-feeding.
I
- 5. The duration of interruption is selected to reduce the maximum dose to a newborn infant to less than 0.1 rem. De actual doses that would be received by most infants would be far below 0.1 rem. He physician may use discretion in the )
recommendation, increasing or decreas'ng the duration of interniption somewhat depending on the woman's concerns about radioactivity or interruption of breast-feeding.
- 6. No consideration of free iodide for this analysis.
- 7. Not applicable (N A) because complete cessation of breast-feeding is assumed.
- 8. A fraction of the adnunistered activity (i.e., 0.41) was treated as intravenous DTPA.
- 9. Treated as Tc-99m DTPA for this analysis.
- 10. Treated as Tc-99m pertechnetate for this analysis.
NUREG-1492 11.2 4 j
[ ,a l
I I
i B.3 REFERENCES l All85 Ahlgren, L S. Ivarsson, L HE86 liedrick, R.H., R.N. Di Simone, Johansson, S. Mattsson, B. Nossim, R.L Keen,1986,
- Radiation 1985,
- Excretion of Radionuclides in Dosimetry from Breast Milk j lluman Breast Milk After the Excretion of Radioiodine and Administration of Radiopharma- Pertechnetate, J. Nect. Med.
27:1569. j ceuticals," J. Nucl. Med. 26:1085. __
l BE73 Berke, R.A., E.C. Hoops, J.C. IIE79 licaton, B.,1979,"The Build Up of l Keretakes, E.L Saenger,1973, Technetium in Breast Milk :
" Radiation Dose to Breast-Feeding pollowing the Administration of Child After Mother has ""'Tc-MAA "Tc"O, Labelled Macroaggregated >
Lung Scan,' J. Nucl. Med.14:51. Albumin," Br. J. Radiol. 52:149.
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