ML20137A240
| ML20137A240 | |
| Person / Time | |
|---|---|
| Issue date: | 02/28/1997 |
| From: | Mcguire S, Stewart Schneider NRC OFFICE OF NUCLEAR REGULATORY RESEARCH (RES) |
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| NUREG-1492, NUDOCS 9703200259 | |
| Download: ML20137A240 (79) | |
Text
Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material Fina Report
- U.S. Nuclear Regulatory Commission Office of Nuclear Regulatory Research S. Schneider, S. A. McGuire
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AVAILABILITY NOTICE i
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a i
Regulatory Analysis on Criteria i
for the Release of Patients 1
i Administered Radioactive Material 4
i i
e 4l Final Report i
i Manuscript Completed: April 1996 Date Published: February 1997
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1 S. Schneider, S. A. McGuire 4
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Division of Regulatory Applications Ofrice of Nuclear Regulatory Research U.S. Nuclear Regulatory Commission Washington, DC 20555-0001 l
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ABSTRACT I
This regulatory analysis was developed to respond (the status quo), primarily due to increased health to three petitions for rulemaking to amend care costs associated with more patients remaining 10 CFR parts 20 and 35 regarding release of in the hospital than under the current patients administered radioactive material. The activity-based requirements. The evaluation also petitions requested revision of these regulations to demonstrates that adoption of the 5-miliisievert remove the ambiguity that existed between the (0.5-rem) dose limit under Alternative 3 v ould 1-millisievert (0.1 rem) total effective dose result in a higher net value to the public equivalent (TEDE) public dose limit in Part 20, compared to Alternative 2 (the status quo),
adopted in 1991, and the activity-based release primarily due to lower health care costs and the limit in 10 CFR 35.75 that, in some instances, increased psychological benefits to patients and would permit release of individuals in excess of their families by permitting earlier release from the current public dose limit.
the hospital.
Three alternatives for resolution of the petitions Based on this analysis, the decision was made that were evaluated. Under Alternative 1, NRC would adoption of the 5-millisievert (0.5-rem) TEDE
- amend its patient release criteria in 10 CFR 35.75 limit is consistent with the provisions in 1
to match the annual public dose limit in Part 20 10 CFR 20.1301(c), and the recommendations of of 1 millisievert (0.1 rem) TEDE. Alternative 2 the International Commission on Radioiogical I
would maintain the status quo of using the Protection that an individual be allowed to receive activity-based release criteria currently found in annual doses up to 5 millisieverts (0.5 rem) 10 CFR 35.75. Under Alternative 3, the NRC TEDE under certain circumstances. Further, it would revise the release criteria in 10 CFR 35.75 no longer restricts patient release to a specific to specify a dose limit of 5 millisieverts (0.5 rem) activity, and therefore, permits release of patients TEDE.
with activities that are greater than currently allowed. The primary benefit is in reduced The evaluation demonstrates that adoption of hospital stays that provide emotional benefits to Alternative 1 would be considerably more patients and their families, and result in lower expensive to the public compared to Alternative 2 health care costs.
i iii NUREG-1492
CONTENTS 3
i
. ABSTRACT.
.. 111 FOREWORD.
ix 4
ACKNOWLEDGEMENTS.
xi 1 STATEMENT OF THE PROBLEM...
I 2 OBJECTIVE OF THE RULEMAKING 2
i l
3 ALTERNATIVES.
.2 1
4 CONSEQUENCES.
2 i
4.1 Current Uses of Radiopharmaceuticals.
.2 t'
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 i
f 4.1.2 Therapeutic Administrations...
.6 4.1.2.1 RadiopharmaceuticalsUsed in Therapy 6
4.1.2.2 Radioactive Materials Used in Permanent Implants (Brachytherapy)..
9 i
j 4.1.2.3 Summary of Therapeutic Administrations.....
10 2
'1 4.2 Assessment of Doses to Individuals Exposed to Patients Administered Radioactive Materials 10 4.2.1 Methodology for Calculating External Gamma Dose.......,,
10 4.2.1.1 Occupancy Factor I1 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 4.2.2.1 Internal Exposure Pathways.
14 4.2.2.2 Measurements of Internal Exposure 15 4.2.3 Estimate of Maximum Likely Doses to Individuals Exposed to Patients...
16 4.2.3.1 Diagnostic Procedures.
16 4.2.3.2 Therapeutic Procedures.
16 4.2.4 Assessment of Doses to Breast-FeedingInfants.
16 4.2.4.1 Internal Dose..
19 4.2.4.2 Extemal Dose...
19 y
I 4.2.4.3 Special Considerations for lodine-131 Sodium lodide.
19 4.2.4.4 Summary of Doses to Breast-Feeding infants 20 4.2.5 Collective Dose
. 21 I
l 4.2.5.1 Collective Dose to Individuals....
. 21 4.2.5.2 Collective Dose to Breast-Feeding Infants...
. 24 4.3 Value Impact Analysis.
24 l
4.3.1 Estimates of the Potential Costs 24 4.3.1.1 Estinates of the Direct Costs of Patient Retention 24 4.3.1.2 Derivation of Indirect Costs.,.
26 4.3.1.3 Evaluation of Psychological Costs 27 4.3.2 Costs and Benefits of Alternatives
. 27 i
l 4.4 Evaluation of the Alternatives With Respect to Accepted Radiation Protection Principles 28 5 DECISION RATIONALE.....
28 d
)
6 IMPLEMENTATION 29 30
)
7 REFERENCES.
APPENDIX A - Parameters and Calculations for Determining Release Quantities and i
Dose Rates for Radionuclides Used in Medicine A.1 APPENDIX B - Parameters and Calculations for Determining Instructions to Patients.Who Are Breast-Feeding.
.. B.l' B.I Calculational Method.
. B.1 B.2 Results
., B.3 B.2.1 Biokinetic Data for Excretion of Radiopharmaceuticalsin Breast Milk..
. B.3 i
B.2.2 Radiation Dose Estimates
. B.3 B.3 References.
B.25 Tables 4.1 Estimated Number of Diagnostic RadiopharmaceuticalProcedures 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
4.3 Age and Sex Distribution of Patients Having Nuclear Medicine Examinations 6
NUREG 1492 vi
4.4 Number of Annual Therape'itic Administrations in the U.S. (significant gamma-emitting radionuclides only)
I1 4.5 Family Doses from Patients Treated with Iodine-131 for Thyroid Carcinoma 12 4.6 lodine-131 Biological Retention and Elimination Parameters for Hyperthyroidism, Thyroid l
Ablation, and Thyroid Cancer.
14 4.7 Maximum Likely Doses to Total Decay to Exposed Individuals from Diagnostic Procedures.... 17 4.8 Maximum Likely Doses to Total Decay to Exposed Individuals from Therapeutic Procedures Assuming No Hospitalization..
18 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 Limits of 1,110 megabecquerels(30 millicuries) or 0.05 millisievert (5 millirems)/hr...
22 i
4.11 Estimates of Collective Dose from Therapeutic Radioiodine Procedures for Alternative 3:.
Annual Limit of 5 millisleverts (0.5 rem)..
23 4.12 Duration of Retention per Therapeutic Procedure.....
25 4.13 Annual Attributes of Alternatives 1,2, and 3 27 l
4.14 Annual Costs and Benefits of Altematives I and 3 Compared to Alternative 2 (The Status Quo).
28 A.1 Half-Lives and Exposure Rate Constants of Radionuclides Used in Medicine A.1 A.2 - Exposure Rate Constants, Release Activities, and Release Dose Rates A.2 B.1 Effective Dose Equivalents to Newboms and One-Year-Olds from infant's intake of Radiopharmaceuticals
.. B.4 B.2 Excretion Fractions and Biological Half-Lives for Radiopharmaceuticals Excreted in Breast Milk.
.. B.5 B.3 Biological and Physical Parameters Used to Calculate the Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticalsin Breast Milk... B.8 B.4 ' Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticalsin 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-Feeding and Recommendations on Interruption of Breast-Feeding.
.. B.23 vli NUREG-1492
FOREWORD l
This regulatory analysis was developed to respond extensive information about the radionuclides to three petitions for rulemaking to amend used for the diagnosis or treatment of disease.
i 10 CFR parts 20 ar.d 35 regarding release of patients administered radioactive material. The This report represents a compilation of this, and petitions requested revision of these regulations to other information on the release of patients remove the ambiguity that existed between the administered radioactive materials, such as the t
1-millisievert (0.1-rem) total effective dose estimate of maximum likely doses to individuals equivalent (TEDE) public dose limit in Part 20, exposed to these patients, assessment of doses to adopted in 1991, and the activity-based release breast-feeding infants, the corresponding collective doses, and the costs and benefits of a release en,tena limit in 10 CFR 35.75 that, a. some matances, would permit release of individuals in excess of that is dose based compared to one that is activity based.
the current public dose limit.
This report contains information on the release of patients administered radioactive material that was In order for the NRC staff to assess the costs and considered by the NRC staff for the rulemaking on benefits associated with a change in the criteria radiological criteria for patient release. The for the release of patients administered results, approaches and methods described in this radioactive materials, it was necessary to obtain final NUREG are provided for informadon only.
Bill M. Morris, Director Division of Regulatory Applications Office of Nuclear Regulatory Research ix NUREG-1492
ACKNOWLEDGEMENTS Much of the statistical and technical information P. Paras, Ph.D., Food and Drug required for this analysis is not available in the Administration, Center for Devices and open literature. In such instances, information Radiology Health, Rocl.ville, MD was obtained directly from technical experts. The following individuals are acknowledged for their cooperation and contribution of technical M. Pollycove, M.D., Visiting Medical information and data.
Fellow, U.S. Nuclear Regulatory Commission, Washington, DC R. Atcher, Ph.D., Radiation and Cellular Oncology Department., University of G.E. Powers, Ph.D., Office of Nuclear Chicago, Chicago, IL Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC K. Behling, S. Cohen and Associates, McLean, VA M. Rosenstein, Ph.D., Food and Drug Administration, Center for Devices and U. H. Behling, S. Cohen and Associates, Radiology Health, Rockville, MD 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 D. Goldin, S. Cohen and Assoc. tes, Advisory Committee on Medical Use of ia McLean, VA Isotopes) Director, Division of Nuclear Medicine, Mallinckrodt Institute of W.R. Hendee, Ph.D., Dean of Research' Radiology, Washington University Medical Medical College of Wisconsm, Milwaukee, WI Center, St. Louis, MO P. Holahan, Ph.D., U.S. Nuclear Regulatory M.G. Stabin, Ph.D., CHP, Radiation Commission, Washington, DC Internal Dose Information Center, Oak Ridge Institute for Science and Education, C. Jacobs, President, Theragenics, Oak Ridge, TN i
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 and Director, D, sion of Health Physics, Information Center, Oak Ridge Institute for m
Milton Hershey Medical Center, Hershey, PA Science and Education, Oak Ridge, TN R. Nath, Ph.D., Professor of Yale K. Suphanpharian, Ph.D., President, Best University, School of Medicine, and Industries, Springfield, VA 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 xi NUREG-1492
1 1
1 STATEMENT OF THE submitted by Dr. Carol S. Marcus (PRM 20-20, l
1 PROBLEM 56 FR 2WS), requested thaube NRC 1
(1) Raise the annual radiation dose limit in 10 CFR 20.1301(a) for individuals exposed to Each year in the United States, radioactive radiation from patients receiving radiopharma-pharmaceuticals or compounds or radioactive ceuticals for diagnosis or therapy from 1 milli-implants are administered to roughly 8 to sievert (0.1 rem) to 5 millisieverts (0.5 rem).
9 million patients for the diagnosis or treatment of disease. These people can expose others (2) Amend 10 CFR 35.75(a)(2) to retain the around them to radiation until the radioactive 1,110-megabecquerel (30-millicurie) limit for material has been excreted from their bodies or i dine-131 (I 131), but provide an activity has decayed away, limit f r other radionuclides consistent with the calculational methodology employed in NRC's patient release criteria in 10 CFR 35.75, the National Council on Radiation Protection
- " Release of Patients or Human Research Subjects and Measurements (NCRP) Report No. 37, Who Have Rece@ived Therapeutic Amount recaW1 nsin c anagement oMadents Containing Radiopharmaceuticals or Permanent Implants, are as follows:
Radionuclides" (NCRP70).
(a) A licensee may not authorize release from confinement for medical care any patient or (3) Delete 10 CFR 20.1301(d), which requires human research subject administered a licensees to comply with provisions of EPA's environmental regulations in 40 CFR Part 190 l
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 or (2) The activity in the patient or the human research sobject is less than College of Nuclear Medicine (ACNM) (PRM-35-10,'
57 FR 8282, as revised by PRM-35-10A, 30 millicurics; (b) A licensee may not 57 FR 21043), requested that the NRC:
authorize release from confinement for medical care of any patient or hmnan (1) Adopt a dose limit of 5 millisieverts (0.5 rem) research subject administered a permanent for individuals exposed to patients who have implant until the measured dose rate from been administered radiopharmaceuticals.
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 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 i
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)
However, when 10 CFR Part 20 was issued, there dealing, in part, with these same issues was submitted was no discussion in the supplemental information by the American Medical Association (AMA).
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.
Because 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.
= _
2 OBJECTIVE OF THE controlling requirements for determining when a patient may be released from the RULEMAKING licensee,s control, o Alternative 3: 5 millisieverts (0.5 rem) total effective dose cauivalent 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 appropriate, the patient release criteria in 5 millisieverts (0.5 rem) to an individual 10 CFR 35.75.
exposed 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 favored an annual dose limit of 5 millisieverts 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 the regulatory approach to be pursued in administration of radiopharmaceuticals or 10 CFR 35.75. To evaluate the issues raised by implantation of a radioactive source to destroy 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 e Alternative 1: 1 millisievert (0.1 rem) total Radiopharmaceuticals effective dose eauhalent Radiopharmaceuticals can be defined as " drugs" This alternative evaluates a dose limit of that are radioactive. Although radiopharma-1 millisievert (0.1 rem) to an individual ceuticals, diagnostic or therapeutic, may be 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 from the licensee's control.
purpose to exert any pharmacological action.
e Alternative 2: < 1.110 megabecouerels Radiopharmaceuticals are generated from two (30 millicuries) or < 0.05 millisievert soura nuclear reactors and accelerators.
(5 millirems)/hr at 1 meter Nuclear reactors can produce radionuclides through neutron capture reactions (e.g., (n, y),
In this alternative, the current patient release (n, p), and (n, or)), as well as by nuclear fission criteria in 10 CFR 35.75 are evaluated as the (n, f). Other radiopharmaceuticals are accelerator NUREG-1492 2
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 subsequent RED 2 Some radiopharmaceuticals may be produced by study reflect information obtained by mail survey either reacter 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.
modme-125 has m the past and continues to be Although his survey was specifically directed to produced by reactors, the production of thyroid examinations, survey data also prosided 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 4.1.1 Diagnostic Administrations summarized in Table 4.1 and represent hospital data only. However, the exclusion of non-hospital 4.1.1.1 Estimates of the Number of Diagnostic facilities should not significantly affect the Procedures Performed anuracy of estamates since less than 1 percent of all nuclear medicme procedures are performed Estimates regarding the frequency and total utside hospitals (JO83). Inspection of Table 4.1 number of diagnostic nuclear medicine procedures
- I' ***al op rtant trends. While the total have been reported over the years in several number of diapostic procedures has shown a studies reviewed and analyzed by Mettler, et al.
general increase, the number of specific (ME85). Among the earliest data reported was a pr cedures has in some cases dramatically study supported by the American College of increased or decreased. By 1982, there were Radiology (ACR75), which reflects data collected I"**'. radionuclide brain imaging examinations in 1972 by J. Lloyd Johnson Associates.
than m 1972, undoubtedly due to replacement by Additional data for the years 1973 and 1975 were c mPuterized tomography (ME85). For the same obtained in a similar fashion and also published in Period, liver tmagmg mereased tenfold. The the American College of Radiology Manpower largest percent merease mvolves cardiovascular
^
Survey (ACR82).
unagmg, which increased from an estimated 25,000 procedures in 1972 to about 950,000 in In 1975, the Bureau of Radiological licalth 1982. Other procedures such as renal, lung, and (BRH; now the Center for Medical Devices and tumor imagmg have experienced only modest increases in numbers.
Radiological Health, CDRH) of the United States Food and Drug Administration initiated a p!!ot study that surveyed information reported by six A search of the open literature revealed no recent hospitals to the Medically Oriented Data System comprehensive studies to assess more current U.S.
(MODS). This project was later expanded to use of radiopharmaceuticals. It is generally include 26 stratified hospitals that provided data thought, however, that the frequency and usage of for 1977 and 1978 (FDA85).
radiopharmaceuticals have stabilized because of the competing technologies of computerized Comprehensive data on 1980 diagnostic imaging tomography, magnetic resonance imaging, and procedures were obtained by J. Lloyd Johnson gray-scale ultrasound (personal communication, Associates by mail questionnaire using a stratified F.A. Mettler, March 1993). For this report, the random sample of general hospitals and selected most recent RED 2 frequency distribution and the office practices in the U.S. (JO83). The sample cumulative frequency of 16 diagnostic nuclear included 6,109 hospitals and was estimated to medicine procedures per one-thousand population reflect about 90 percent of the total diagnostic will be used to estimate current usage. Table 4.2 imaging examinations. Additional studies were provides frequency estimates of diagnostic conducted by the BRH for the years 1980,1981, procedures adjusted to reflect the 1993 U.S.
and 1982. The hospital-based survey was called population, which is projected at 256,466,000 by the Radiation Experience Data (RED 1 and the United States Bureau of the Census.
Table 4.1 Estimated Number of Diagnostic Radiopharmaceutical Procedures Performed in the United States Between 1972 and 1982 Year 1972 1973 1975 1978 1980 1980 1981 1982 1982 Source Examination Type ACR ACR ACR MODS Johnson RED 1 RED 2 RED 2 Parker Brain 1260*
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 Thyroid 356 460 627 699 650 506 664 677 533 Urinary 108 122 154 205 200 164 402 236 Tumor 10 14 22 166 130 125 121 Cardiovascular 25 33 49 160 580 558 708 950 Other 686 294 338 120 120 368 Total 3339 3510 4803 6411 5830 6374 7199 7401 7690 (16)'
(17)
(22)
(29)
(26)
(28)
(31)
(32)
(33)
Source: ME85.
- Numbers not in parenthesis indicate number of examinations x 1,000.
t 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 (I-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 43. For the period of approximately 8.2 million diagnostic examinations observation, more than three-fourths of all nuclear i
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 (Xe-133),
exception of the youngest age category, the about 5 percent use thallium 201 (T1-201), about percentage of females exceeded males.
Table 4.2 Estimated Rt.diopharmaceutical Use for Diagnostic Procedures in the United States in 1993*
1 Typical Activity Number of Examination Type per Examination Examinations (Radiopharmaceutical)
(MBq)
(mCl)
(x 1,000)
Brain
- Tc-99m DTPA 740 (20) 450 4
l Tc-99m 0 (Pertechnetate) 740 (20) 450 4
Hepatobiliary
- Tc-99m IDA 185 (5) 198 Liver
- Tc-99m Sulfur Colloid 185 (5) 1,578 Bone
- Tc-99m Phosphate 740 (20) 2,007 Lung Perfusion
- Tc-99m MAA 185 (5) 871 Luna Ventilation j
- Xe-133 370 (10) 449 Tlwroid l
- Tc-99m O. (Pertechnetate) 185 (5) 600
- I-123 11.1 (0.3) 75
- I-131 3.7 (0.1) 75 Renal
- Tc-99m DTPA 740 (20) 157
- I-131 Hippuran 9.3 (0.25) 105 Cardiovascular Tc-99m RBC 740 (20) 421
- Tc-99m Phosphate 740 (20) 211
- TI 201 Chloride 111 (3) 421 Tumor
- Ga-67 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
4 2
Table 4.3 Age and Sex Distribution of Patients llaving Nuclear Medicine Examinations Male Female Total Age
(%)
(%)
(%)
I
< 15 0.9 0.7 1.6 13 - 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: M E86.
4.1.2 Therapeutic Administrations is most commonly associated with Graves' Disease. Graves' Disease is an autoimmune Therapeutic use of radioactive materials involves disease in which the body's own immune system is two distinct approaches. The first involves the directed against cellular and secretory products of oral, intravenous, or intracavity administration of the thyroid gland. Hyperthyroidism can also be a radiopharmaceutical that may subsequently be the result of excessive hormone production by a distributed, concentrated, retained, and eliminated single " toxic" nodule, thyroid carcinomas, and by physical, chemical, and metabolic actions medications inclusive of potassium iodide.
occurring within the body. The second approach Hyperthyro.dism is not a condit. ion reportable to i.
involves the implantation of radioactive sources (i.e., seeds) directly into a solid tumor. While Public health agencies. As a resul, data on rates t
f ccurrence and treatment must be mferred.
both temporary and permanent implants are performed, all patients receiving temporary incidence of hyperthyroidism ts reported at 3 per implants are hospitalized until the implants are 10,000 adults per year, with peak mcidence removed. Thus, only permanent implants are ccurring between 30 and 50 years of age (DG79).
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 Herapy assumed that about 75 percent of the United States population (approximately 191,500,000 The.m-vivo use of radiopharmaceuticals.m 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 lethal radiation doses to the selected target tissue.
year require medical treatment for Most destrable are beta emitters that can deliver hyperthyroidism.
intense irradiation of target cells while sparing the surrounding tissues. In contrast to diagnostic Although medical treatment may in some cases 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 applications are described below, per year.
Ilyperthyroidism In the past, therapeutic quantities of iodine-131 for treatment of hyperthyroidism tended to be of Hyperthyroidism is characterized by an increased a magnitude (185 to 550 megabecquerels production of thyroid hormone. Hyperthyroidism (5 to 15 millicuries)) that would reduce the NUREG-1492 6
hormone production of the hyperactive thyroid 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.
therapeuticaHy induced euthyroidal condition (normal or healthy thyroid) deteriorated to one of hypothyroidism requiring thyroid hormone nyro d Cancer replacement therapy. As a result, today hyperthyroid therapy also involves the use of There is no nationwide cancer registry that iodine-131 to ablate the thyroid. Approximately accurately defines the number of new cases of 50 percent of all hyperthyroid patients undergo cancer diagnosed each year. However, the ablation (personal communication, M. Pollycove, American Cancer Society (ACS) annuaUy January 1996). Typically, activities in the range publishes data on cancer incidence and patient from 550 to 1,110 megabecquerels (15 to survival based on information provided by the 30 millicuries) are used but about 2 percent of au National Cancer Institute's Surveillance, 1
patients require as much as 2,220 megabecquerels Epidemiology, and End Results (SEER) program.
(60 millicuries), the maximum typically
{
administered. Such doses quickly result in the The ACS estimates of United States cancer cases total loss of thyroid ft.nction and the patient is diagnosed for 1992, are based on age-specific 4
given hormone replacement therapy from the incidence rates from the SEER program for 1986 onset (personal communications, F. A. Mettler, to 1988 applied to the Census Bureau's population March 1993 and M. Pollycove, January 1996).
projections for 1992. The ACS's estime'e of new thyroid cancers in 1992, is 12,500 (ACS93). This
'Ihyroid Nodules report assumes that 100 percent of these cases will be treated by the surgical removal of thyroid Single or multiple nodules of sufficient size may gland tissue (i.e., thyroidectomy). Following cause obvious enlargement of the thyroid. A surgery, about 20 percent of these cases will not nodule (s) refers to a replacement of the normal require additional thyroid cancer therapy but homogeneous cytostructure of the thyroid with a about 80 percent will require additional histologic pattern ranging from colloid-filled cysts therapeutic administrations of iodine-131 to 3
and colloid adenomas to follicular adenomas.
eliminate residual thyroid cancer tissue (personal Since the incidence is 4 to 5 times as great in communication, M. Pouycove, January 1996).
women as in men, and since it develops and Therefore, this report assumes that about progressively increases in size during life, it is 10,000 cases per year will be treated with j
most frequently found in females 50 to 70 years of therapeutic doses of iodine-131.
j age. It is not uncommon for nodules to remain undetected until a post-mortem examination.
The quantities of iodine-131 used in thyroid cancer therapy depend upon the type of cancer, Small nodules in cuthyroid subjects require no the status of the cancer, and the degree of uptake therapy. If the gland is grossly enlarged and and retention of iodine-131 by residual cancerous causes a cosmetic problem or tracheal thyroid tissue. As a result, current therapeutic compression, treatment may be indicated along quantities range from 1,850 to with thyroid hormone replacement therapy.
11,100 megabecquerels (50 to 300 millicuries)
(personal communications, F.A. Mettler and K.L.
A small percentage of thyroid nodules tend to Miller, March 1993). The typical quantity produce thyroid hormones uncontrollably and in administered is 5,500 megabecquerels excess (i.e., the nodule is not under the regulatory (150 millicuries) (personal communication, M.
control of the pituitary gland and is clinically Pouycove, January 1996).
referred to as toxic nodular goiter). The presence of these autonomously functioning thyroid nodules leads to hyperthyroidism (i.e., thyrotoxicosis).
Herapy for Polycythemia Vera Toxic nodular goiter, like Graves' Disease, may be Since the introduction of radiophosphorus (P-32) treated surgicauy (i.e., thyroidectomy) or by in 1936, patients with polycythemia vera have been therapeutic dose (s) with radioactive iodine.
treated successfully with this radioisotope to control 7
i rather than cure this disease. Polycythemia vera Intra-Arterial Therapy is a relatively rare disease that is characterized by an autonomous proliferation of marrow cells Some primary tumors as well as metastatic lesions leading to an over production of red blood cells, are highly vascularized. Direct arterialinjection white blood cells, and platelets. Typically, with insoluble radiolabelled particulates that lodge phosphorous-32 is administered intravenously in in arterioles and capillaries of the tumor is the doses of 111 to 185 megabecquerels (3 to basis of this form of therapy (EH87, ZI84).
Insoluble carriers of radionuclides that have been 5 millicuries) per treatment over a period of time with average cumulative quantities of clinically tested include iodine-131-labelled oil 740 megabecquerels (20 millicuries) per patient.
contrast medium, iodine-131-lipoidal or -ethiodol (PA87), yttrium-90-glass microspheres (HE88),
and yttrium-90 (Y-90) resin particles (ROE 90).
j Bone Therapy S nce these therapies are so seldom used, their
]
impact may be ignored in this analysis.
)
Since the use of radioactive strontium for the treatment of bone metastases was first described Intracavitary Tumor Herapy in early 1942 (PE42), bone therapy has included other radionuclides. Bone therapy may involve For tumors that are spread over the scrosal the treatment of primary bone tumors such as linings of the body cavities or for ascites tumors, ne approach to dehvermg therapeutic doses of l
osteosarcoma (B127) in which bone-seeking radiation is to inject the radiopharmaceutical radiopharmaceuticals are in fact tumor seeking.
directly mto the body cavity. For this approach, Bone therapy may also be the treatment of painful coll ids, chelates, and, more recently, monoclonal l
skeletal metastases, which may be palliated by antibodies labelled with gold-198 (Au-198),
l bone-seekm.g radionuclides. Although the phosphorous-32, yttrium-90, or iodine-131 can be I
literature references the palliative and tumor used.
therapeutic use of % w rndionuclides (phosphorous-32: CH80, RO77; strontium-89 Initially, gold-198 colloids were used, but (Sr-89): ble8, KIE7, RO87, ROE 90, S185; phosphorous-32 is now preferred due to its longer rhenium-186 (Re.186): KE87, MA88, SC90; half-life, more energetic beta particles, and the samarium-153 (Sm-153): LA90, TU89), there are absence of gamma radiation. Intracavitary no databases and no studies have been performed radionuclide therapy with phosphorous-32 in that would allow quantitative estimates regarding quantities of 185 to 370 megabecquerels (5 to the number of patients given bone therapy with 10 millicuries) has been applied to malignancies radiopharmaceuticals. These other therapies are invoMng the pleural, pericardial, and peritoneal i
performed so seldom that they have negligible cavities (JA81, KA81, MA78),
impact in comparison with the radiolodines.
More recently, iodine-131-or yttrium-90-labelled tumor-associated monoclonal antibodies have Herapy with Radiolabelled Cells been used in intracavitary therapy (F189, PE86, RI90) in doses of 740 to 2,220 megabecquerels For lymphoid cell malignancies, the tumor cells (20 to 60 millicuries). Superiority of monoclonal (i.e., lymphocytes) may retain their ability to antibodies over colloids is expected due to the migrate and recirculate into the lymphoreticular enhanced affinity of the labelled antibody for the tissues (i.e., spleen, liver, bone marrow, and lymph target cells. At present, these therapies are rarely l
nodes). The harvesting, labelling, and reinjection used and thus have no impact in comparison with of lymphocytes has been demonstrated to deliver radioiodines.
therapeutic levels of radiation doses to tumors of the lymphoreticular system (CO87). Indium-114-Radioimmunotherapy labelled lymphocytes have a potential therapeutic role in the management of lymphoma, and clinical Radioimmunotherapy involves the use of studies are underway. Because use of this new radiolabelled antibodies directed against therapy is not widespread, it will not be tumor-specific antigens such as the J
considered any further in this analysis.
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, particularly 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 administered 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 The radionuclides primarily used in permanent (10 to 30 millicuries) have been used.
implants are iodine-125 and palladium-103. Less frequertly 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 radioimmunotherapy. 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 for 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 (CIE9, 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 rays.
breast cancers (RU92), and tumors of the head, Brachpherapy can be divided into temporary 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 replacement 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 brachytherapy, 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 (PO90). 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 J
-=-.
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.i.2.3 Summary of Therapeutic Gold 198 implants have been used in a few Administrations instances of prostate cancer (CA88, FR88). The 4
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 estimates of the numbers its use in recent years to fall into disfavor and be of each therapy performed annually.
used only rarely (CA87).
4.2 Assessnient of Doses to A thorough search of the literature and personal communications with several prominent members Individuals Exposed to of the medical and scientific community (see Patients Administered Acknowledgements) indicates that there is no Radioactive Materials 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 in each of th alternauws,it is necessary to how the acknowledgments to this report does support the magnitude of doses that could be received by the following,~
an individual exposed to a patient who has been administered radioactive materials. While 1.
permanent implants are currently considered exp sure can occur na any of the eh,mmau,on an appropriate treatment for only a few sites Pathways by which radionuclides are removed of solid tumors; from the body (e.g., exhalation, feces, sahva, sweat, urine, and possibly vomit), experience 2.
among the cancer sites for which permanent indicates that for todme-131 and other gamma implants are currently employed, prostate cancer represents the overwhelming majority; f*.itters, these pathways will generally be mstgmficant m relation to the doses that can result from exposure to the direct gamma 3.
among the 132,000 annual new cases of prostate cancer (ACS93), only a small yadiation from the patient, with the except,on of mtak from the m, k m breast-feedm, g, fants.
d m
fraction is treated with permanent implants; This section of the report assesses the external and internal doses to individuals, including a breast-feeding infant, exposed to patients who 4.
for the purposes of this analysis, implants ham bn adnumsterd radmach matenals.
involving gold-198 (largely discontinued) and ytterbium-169 (isolated use only) may be ignored.
4.2.1 Methodology for Calculating External Gamma Dose In the absence of documented clinical data, information was sought from the implant vendors The methodology for calculating the external 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 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, ranging from 1,110 to 1,850 megabecquerels
" Precautions in the Management of Patients Who (30 to 50 millicuries). For palladium-103, Have Received Therapeutic Amounts of approximately 1,500 implants are performed Radionuclides" (NCRP70).
NUREG-1492 10
Table 4.4 Number of Annual Herapeutic Administrations in the United States (significant gamma-emitting radionuclides only)
Range of Activities Estimated No. of Therapeutic Radionuclide Administered Administrations Procedure Employed
(!\\1Bq)
(mCl)
(per year)
Thyroid Ablation and 1-131 370 - 2,220*
(10 - 60) 50,000 Hyperthyroidism Thyroid Cancer 1-131 1,850 - 11,100* (50 - 300) 10,000 Permanent implant 1-125 1,110 - 1,850' (30 - 50) 2,000 Permanent Implant Pd-103 2,775 - 4,625t (75 - 125) 1,500 Total 63,500
- Based on personal communications, F. A. Mettler, March 1993 and M. Pollycove, January 1996.
- Based on personal communications, F. A. Mettler and K.L. Miller, March 1993.
' Based on information supplied by implant vendors, August 1993.
To calculate the dose to total decay D(oo), the when most of the dose is delivered 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
'( ' }
contact with a released patient are highly variable (1)
D(=) =
(100 cm)2 and reflect the crucial, but difficult to define, parameters of time, distance, and shielding.
Based on time and distance considerations, it is and for radionuclides with a half life less than or reasonable to conclude that for the overwhelming equal to 1 day majority of released patients, the maximally exposed individual is likely to be the primary care-(2)
Provider, a family member, or any other individual D(a) =
(100 cm)2,
who spends significant time close to the patient.
Based on time, distance, and shielding factors, where P = exposure rate constant for a which describe normal lifestyles of the United point source, R/ mci-h at I cm, States population, it is highly unlikely that doses equal to spending 100 percent of time at a Q, = initial activity of the point source in distance of 1 meter from a patient would result to millicuries, at the time of release, any individualincluding a patient's spouse. As a standard medical practice, patients undergoing T, = physical half-life in days.
therapeutic treatments with radiopharmaceuticals 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 half-lives greater than 1 day, that the individual Given all considerations, a reasonable estimate of likely to receive the highest dose from exposure to the maximal likely dose to an individual exposed the patient would receive a dose of 25 percent of to a patient is 25 percent of the dose to total 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 riay, occupancy factor of 25 percent at 1 meter for the factor 1.0 is used in Equation 2 because the estimating maximal likely exposure is based on the assumption that the time that individuals will authors' professional judgment of time-distance spend near the patient will be limited is not salid combinations that are believed likely to occur 11 NUREG-1492
Table 4.5 Family Doses from Patients Treated with lodine 131 for 'Ihyroid Carcinoma Measured Predicted Total Body Burden Doses to Dose Based on Activity at Time of Family Occupancy Factor of Administered Discharge Members 25% at 1 meter Patient (mCl)
(mCl)
(mrem)
(mrem) 1 210 25.2 80,70,30 386 2
311 26.4 50,20,20 404 3
209 18.4 80,40 282 Sourec: !!A74.
when instructions to minimize time spent close to demonstrates that if reasonable efforts to maintain the patient are given.
distance are not made doses can be higher than predicted by Equation 1.
The occupancy factor of 0.25 at 1 meter is also supported by empirical data. Harbert and Wells Buchan and Brindle (BU71) monitored the doses (HA74) monitored the external dose of 8 family of 54 family members of patients who underwent 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 occupancy factor of 25 percent at 1 meter in totally disregarded. The highest measured dose to Equation 1. The actual doses are far below the a family member was 2.7 millisieverts (0.27 rem),
calculated doses for an occupancy factor of much below the 5-millisievert (0.5-rem) ilmit.
25 percent at 1 meter, indicating that the model The effective occupancy factor at 1 meter was less generally provides a conservative estimate of the than or equal to 0.25 in 45 of the 54 cares (83 dose.
percent). Thus, even in the complete 9bance of instructions, the occupancy factor at 1 meter was Harbert and Wells (HA74) also measured the usually less than 0.25.
external doses to 11 family members of seven hyperthyroid patients. All doses to family in conclusion, both empirical measurements and members were far below 5 millisieverts (0.5 rem).
professionaljudgement 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 Jacobson et al. (JA78) measured the external followed. However, higher occupancy factors are 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 predicted by Equation 1 using an occupancy factor based on Alternative 3 provides an adequate level 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.
NUREG 1492 12
4.2.1.2 Exposure Rate Constant both of which are dependent upon the physical condition of the patient. Table 4.6 pronies the The exposure rate constant P expresses the dose uptake fraction and biological half-life for wh 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 adminis'ered iodine-131, palladium 103 implants, the dose to total decay at considering biological reteNion 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 represcat the dose in Table A.1 of Appendix A. The physical contribution from the thyroidal and extrathyroida!
- 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 coinplete 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
'( ' }
(4)
Effective Half Life D(~) =
+
(100 cm)2 A licensee may replace T, in Equations (1) and
.34.6N,T /2(0.25)
(2) with the effective half-life T,of the 2
radioactive material to demonstrate compliance (100cm):
with the dose limit in the revised 10 CFR 35.75.
T,is characterized by T, and the biological half-life T, of the radionuclide (which accounts for where T,, = effective half-life of the exuathyroidal the biological retention and climination of the component in dsys (based on the radionuclide from the patient's body) according to biological half-l fe T., of the -
the equation thyroidal compoaent),
T, = T' # T'.
(3)
F = extrathyroidal uptake fraction, i
T, + T, T, = effective half-life of the thyroidal 2
component in days (based on the Under the final rule a licensee could authorize on the biological halflife T of the S2 release on a case-by-case basis based on the thyroidal component),
bi logical half-life rather than only the physical o
ialflife of the radiopharmaceutical.
F, = thyroidal uptake fraction, Biolonicr! Metention and Elimination of Iodine 131 P = exposure rate constant for a point source, R/ mci b at 1 cm, For iodine-131, biological retention and elimination are characterized by the fractional Q, = initial activity of the radionuclide in amounts that reside in the thyroid G.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 valid if the release occurs at a specific fractional uptake and biological half-life, the time of administration.
13 NUREG-1492
Table 4.6 lodine 131 Biological Retention and Elimination Parameters for Hyperthyroidism, nyroid Ablation, and Hyroid Cancer
- Extrathyroidal Hyroidal Component Component Uptake Biological Uptake Biological Fraction Half-Life Fraction Half-Life i
Disease F,
Tu (days)
F Tn (days) j 3
l Hyperthyroidism and 0.10 033 0.90 10 Thyroid Ablation 0.20 033 0.80 15 030 033 0.70 20 0.40 033 0.60 20 0.50 033 0.50 25 0.60 033 0.40 40 0.70 033 030 65 Thyroid Cancer G.95 033 0.05 80
- Data taken from ICRP Publications 30 OCRP78),53 GCRP87), and 56 0CRP89), and personal communication, M. Pollycove, March 1996, based on his clinical experience.
4.2.1.4 Tissue Shielding for Permanent Implants the lungs, brain, pancreas, etc., tissue shielding values of similar magnitude can be assumed for in addition to the shielding effects of the source an adult male and female. However, for certain capsule (see 4.2.1.2 Exposure Rate Constant), a implants invoMng primary cancers of the neck significant reduction in the dose and dose rate and head, overlying tissues may provide less than also occurs from the tissue surrounding the 5 HVLs of attenuation. In such instances, it is implant. For a prostate implant, tissues that serve standard practice to provide the patient with a to reduce photon flux about the patient include small portable " shield" which effectively attenuates the soft and bone tissues of the thighs, pelvis, all emissions (personal communications, C. Jacobs, buttocks, abdomen, etc. The linear attenuation 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 a vinyl sheet impregnated with lead and molded 0387 cm and 1.8 cm, and for the 21 kev photon to fit the anatomical surface over the implant.
of palladium-103,0.770 cm-' and 0.9 cm, respectively (JOH83).
For the purposes of this analysis, implants will be 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 Assessment of Internal Exposure (personal communication, J. St. Germain, March 1993). Based on empirical assessment invoMng 4.2.2.1 Internal Exposure Pathways patients with prostate implants, tissue shielding for iodine-125 is likely to exceed 5 or more half-value Upon oral administration or direct injection into layers (HVLs), 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, palladium-103 implants, in which the HVL in distribution, and excretion. Removal of s
tissue is less than 1 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 involving saliva, sweat, urine and vomitus.
NUREG-1492 14
Breast 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 radiciodines. Relatively small administrations of source for internal exposures to others have been radioiodine to a breast feeding women can cause assessed for various excreta pathways (BL71, 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 Air. Exhalation is the principal pathway Contamination through urinary excretion may be for the elimination of radioactive gases such as readily controlled by cautious but reasonable xenon-133, which is used for lung ventilation tests.
hygiene practices.
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 gastrointestinallumen 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 radiciodine 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 megabecquerels (4 to Sweat. Radionuclides present in the extracellular
?0 millicuries) per patient. Of the 39 patients,28 fluid will tend to be excreted in the sweat in
. instructed to take precautionary measures to
- w <
accordance with the fraction that is unbound in mmimize 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 of iodine.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 elimination route, since orally administered dose is negligible compared to the external dose, 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. However, a significant involved, precautions to minimize contamination portion of the administered radionuclide could be should be abandoned."
excreted if vomiting occurs immediately following the administration. In this case the patient In a 1978 study by Jacobson, et al. (JA78), sever, typically would not have been released, and the families were studied in which one family member licensee would be able to limit exposure and clean had been treated with iodine-131 doses ranging up contamination.
from 2% to 5,500 megabecquerels (8 to i
15 NUREG-1492
-..~
1 i
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) was deliver a 1 millislevert (0.1 rem) dose to an
)
determined at discrete time intervals by means of individual exposed to a patient. However, in the j
a pair of 30-inch Nal crystals. Although all family case of iodine-131, the effective half-life of the members proximal to the patient had measurable extrathyroidal component is much shorter than thyroid burdens, dose estimates in nearly all cases the physical-life used to calculate doses.
indicate that internal committed effective dose Therefore, the dose would be much lower than equivalents were always less than 10 percent of the value shown in Table 4.7. Since the doses in the 5-millisievert (0.5-rem) dose limit, even when all cases are much below 1 millisievert (0.1 rem),
l 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 "...
4.23.2 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 calculnions assume an the radiation therapy. Most, however, are concerne.i 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 unwilling 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 elimination sqpuficant external dose and transfer of contanunation provides dose estimates that are significantly less is not a significant contributor to internal dose.
than the model that considers physical half-life only.
Thus, the studies on internal exposures suggest 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 P ysical half-life. Only the therapies involving h
4.2.3 Estimate of Maximum Likely radiciodme 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 with each of the radionuclides used.
If a radiopharmaceuticalis administered to a woman who is breast-feeding an infant, a fraction 4.23.1 Diagnostic Procedures of the quantity administered may be deposited in the breast milk and may be transferred to the The results of the dose calculations for diagnostic infant. In considering the dose to the indisidual procedures are summarized in Table 4.7.
likely to receive the highest dose from exposure to NUREG-1492 16
Table 4.7 Maximum Likely Doses to Total Decay to Exposed Individuals from Diagnostic Procedures Activity per Examination Type Examination
- Gamma Dose' (Radiopharmaceutical)
(MBq) (mCl)
(mSv)
(rem) 1 Brain Tc-99m DTPA 740 (20) 0.13 (0.013) j
- Tc-99m O, 740 (20) 0.13 (0.0 13)
Hepatobiliary
- Tc-99m IDA 185 (5) 0.03 (0.003)
Liver Tc-99m Sulfur Colloid 185 (5) 0.03 (0.003)
Bone
- Tc-99m Phosphate 740 (20) 0.13 (0.013)
Lung Perfusion
- Tc-99m MAA 185 (5) 0.03 (0.003)
Thyroid
- Tc-99m Oa 185 (5) 0.03 (0.003) 131 3.7 (0.1) 0.02 (0.002)
- I-131 (maximum) 370 (10) 1.5 (0.15)
Cardiovascular
- Tc-99m RBC 740 (20) 0.13 (0.013)
- Tc-99m Phosphate 740 (20) 0.13 (0.013)
- TI-201 Chloride 111 (3) 0.04 (0.004)
Renal
- Tc-99m DTPA 740 (20) 0.13 (0.013)
- I-131 Hippuran 93 (0.25) 0.04 (0.004)
- 'Ihe activity is the typical quantity administered per examination (see Table 4.2). The maximum diagnostic activity of I 131 is shown because it yields gamma doses exceeding i millisievert (0.1 rem).
' Calculations assume no biological elimination, no attenuation of gamma rays in air or body of patient, and occupancy factors of 100 percent at a distance of I meter for Tc-99m and 25 percent at a distance of 1 meter for I-131 and T1201.
17 NUREG-1492
Table 4.8 Maximum Likely Doses to Total Decay to Exposed Individuals from Herapeutic Procedures Assuming No llospitalization Gamma Dose Based on Effective flatf-Life
- Gamma Dose Extrathyroidal nyroidal Based on Component Component Therapeutic Activity Physical Uptake Uptake Procedure Administered IIalf Life
- Fraction Fraction Dose (Radionuclide)
(MBq) (mCl) (mSv) (rem)
F, F,
(mSv) (rem)
Hyperthyroidism &
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 0.30 0.45 (0.045) 1,110 (30)t 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 0.30 1.35 (0.135) 2,220 (60) 9.2 (0.92) 0.40 0.60 4.02 (0.402) 0.50 0.50 3.66 (0366) 0.60 0.40 3.48 (0.348) 0.70 0.30 2.70 (0.270)
Thyroid Cancer
- iodine-131 1,850 (50) 7.6 (0.76) 0.95 0.05 0.62 (0.062) 5,550 (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"
- iodine-125 1,110 (30) 0.54 (0.054)
Effec'ive IIalf-Life Not Applicable to 1,480 (40)t 0.72 (0.072)
Permanent Implants 1,850 (50) 0.90 (0.090)
- palladium 103 2,775 (75) 0.29 (0.029) 3,700 (100)' 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.
- Doses have been calculated for the four thyroidal uptake fractions that characterize the majority of patients treated.
' Typical activity administered.
" These dose values account for the 5 IIVLs of tissue shielding by the pstient and, therefore, are equal to the point source dose in air divided by 32.
NUREG-1492 18
a patient who has been administered a 1 millisievert (0.1 rem). If the sum of the doses radiopharmaceutical, it is necessary to consider in Columns 3 and 4 of Table B.5 (i.e, internal both the internal and external dose to the infant (maximum value) and external doses, respectively) from breast-feeding.
for a radiopharmaceutical exceeds 1 millisievert (0.1 rem), then instructions would be required.
4.2.4.1 laternal Dose 4.2.43 Special Considerations fo Edine 131 The potential internal dose to the breast-feeding Sodium Iodide infant was calculated for the maximum normally administered quantities of commonly used There are specific issues associated with the diagnostic and therapeutic radiopharmaceuticals.
administration of iodine-131 sodium iodide in that The results of the calculations are shown in following both diagnostic and therapeutic Appendix B.
administrations, the dose to a breast-feeding child could exceed 5 millisieverts (0.5 rem) if there was The doses can be represented as a range where no interruption of breast feeding. In particular, if the range covers the minimum and the maximum the woman does not cease breast feeding after transfer of radioactive material from published administration of millicuric quantities of data. The range is due to individual variability iodine-131 sodium iodide, the internal dose to the and measurement variability as indicated by breast-feeding infant could be large enough to concentrations measured id breast milk. Doses cause the infant's thyroid to be sewrely damaged, were calculated for newborn and one-year-old resultingin hypothyroidism. If hypothyroidism infants. Since the doacs for newborn infants are were undiagnosed in very young children, severe higher, those doses were used in the analysis, mental retardation may occur. However, if the The internal dose ranges for commonly used patient was provided instructions to discontinue radiopharmaceuticals assuming no interruption of breast-feeding, as well as being advised of the breast feeding are shown in Column 3 of consequences of not following the instructions, the Table B.5 (see Appendix B). The radionuclides in NRC believes that the probability of a woman the table that are not regulated by the NRC failing to cease breast-feeding after being (e.g., Ga-67) are omitted from further administered iodine-131 sodium iodide is small, consideration in this analysis.
For example, in 1990 an administered dosage of 185 megabecquerels (5 millicuries) of iodine-131 4.2.4.2 External Dose sodium iodide to a patient resulted in her breast-fed infant receiving an unintended radiation To determine a realistic estimate of the external dose of 300 grays (30,000 rads) to the infant's dose to total decay to the infant during breast thyroid gland. This dose would result in ablation feeding, an occupancy factor must be selected that of the infant's thyroid. This situation was specifically reflects the variables involved. It can recognized in 2 days, which allowed prompt action be assumed that the average infant feeds for a to be taken thereby reducing potential 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 consequences such as mental retardation. The in an occupancy factor of 16 percent. Breast-NRC is aware of two other cases that occurred feeding requires close contact, the analysis uses during 1991 and 1995. In eac'a of these cases, 20 centimeters as the distance between the infant there was a breakdown in con.munications, rather and the source. Also, since only the physical than lack of intent to preven'. breast-feeding. This half life is considered, the analysis is conservative.
rule might therefore be pcted to provide a The results are shown in Column 4 of Table B.5 benefit by reducing the probability of a woman assuming no interruption in breast-feeding.
breast-feeding an infant after administration of large quantities of iodine-131.
The final rule requires that instructions, including written instructions, on maintaining the doses to In some cases, instructions to interrupt or other individuals as low as is reasonably discontinue breast-feeding may not be effectively achievable be given to the released patient if the communicated. To deal with this issue, the NRC dose to another individual is likely to exceed considered a range of options which varied from i
19 NUREG-1492
l 1
maintaining the status quo to the extreme option cost for the extreme option is 400 x 7 x $1,000 i
of confining a woman for a period of time after
= $2.8 million. In addition, there would be j
administration of millicuric quantities of associated costs for providing women with 3 -
- iodine 131 sodium iodide to ensure her milk instructions and information as to the need for j
production has stopped. Included within this hospital retention The circumstances of a woman
]
range of options was the option to enhance choosing to ignore the warning that breast-feeding communication between the licensee and woman would cause significant harm to the infant and to j
regarding instructions to interrupt or discontinue continue to breast-feed are considered to be very breast-feeding before the woman is released from rare. As stated above, NRC is not aware of any the hospital. It is estimated that approximately instance where this has occurred. Therefore, the 400* breast-feeding women could be administered extreme option was not selected because of the millicuric amounts of iodinc.131 sodium iodide each negative psychological impact to both the woman year for diagnosis and treatment of thyroid disease, and infant, as well as the high annual dollar cost.
The option of maintaining the status quo does not Regarding the preferred option to enhance provide the assurance that instructions will be communication, although instructions to keep provided to a breast-feeding woman and could doses to household members and the public as still allow for a breakdown in communications.
Iow as is reasonably achievable are currently As indicated above, the NRC is aware of three required for radiopharmaceutical therapy in cases of unintended exposure to a breast-feeding 10 CFR 35315(a)(6), there is no requirement child during the last five years. There would be specific to the dose from breast-feeding.' To no costs associated with this option.
enhance communications, amended 10 CFR 35.75(b) will require licensees to provide guidance on the At the other end of the range, for the extreme interruption or discontinuation of breast-feeding option, a woman would remain in the hospital and information on the rationale for following the until she stopped producing milk. However, this guidance. Compliance with the regulation option would result in psychological impacts to provides NRC with confidence that the licensee both the woman and breast-feeding infant, by will give the instructions to breast-feeding women requiring them to be physically separated for and it is expected that almost all women will some period of time, which are not quantified by follow instructions to interrupt or discontinue this analysis. This option was also considered to breast-feeding to protect their children from be impractical as it would be difficult for a potentially harmful effects. The NRC is not medical institution to separate a woman and aware of any instances where instructions were breast-feeding child. That is, this option does not given to the woman but she ignored the warning prevent the breast fed child from being brought and continued breast-feeding a child. Since the into the patient's room, nor does it address the estimated costs per patient for providing situation of the patient releasing herself against instructions and recordkeeping are $22 and $17, medical advice. Also, to require cessation of respectively (see 43.1.1 Estimates of the Direct breast-feeding after administration of iodine-131 Costs of Patient Retention), the estimated costs sodium iodide by hospital retention, or prior to for this option would be about $16,000 per year.
administration (to avoid hospital retention),
Therefore, the option to enhance communication directly impacts the practice of medicine, since it is selected as the preferred option. It should be would in effect dictate when a treatment could be noted that since the extreme option was not given. It is estimated that each woman would selected for administrations of millicurie remain in the hospital for an average of 7 days at quantities, then it would follow that for microcurie a cost of $1,000 per day. The estimated annual quantities it would not be cost effective.
^
4.2.4.4 Summary of Doses to Breast Feeding
- The number of breast-feeding women was Infants determined as follows: 60,000 patients administered millicuric quantities of iodine-131 The dose to the breast-feeding infant can be sodium iodide x 0.135 child bearing age x 0.05 controlled by giving the woman instructions, as breast-feeding = 405 patients administered required by the revised 10 CFR 35.75, to millicuries of iodine who could be breast-feeding.
discontinue or to interrupt breast-feeding as NUREG-1492 20
appropriate. The decision to require instructions about half as much time near the patient. There as shown in Column 5 of Table B.5 is based on might also be about four other people who will both the external and internal dose to the nursing average about a quarter as much time near the infant. It can be seen from Column 4 that for patient as the maximally exposed individual. The some radiopharmaceuticals the external dose from sum of the collective dose to all these people is breast-feeding can be a significant part of the total 3 times the dose to the maximally exposed individual.
dose. The duration of the interruption shown in This situation could represent a typical family and Column 6 is selected to reduce the maximum dose friends. Of course some patients will spend more to a newborn infant to less than 1 millisievert 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 j
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 by Equation 4) Tables 4.9, To evaluate each alternative, it is also necessary 4.10, and 4.11 present the estimates 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 administered radioactive materials. To calculate the typical administration of iodine-131 for thyroid precisely the collective dose that would be ablation, this analysis uses 1.73 millisieverts 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 majority 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 we believe is adequate for the (2,220 megabecquerels (60 millicuries)), was purposes of this rulemaking.
determined to be 3.47 millisieverts (0347 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 collective doses. Implants using iodine-125 are provided patients, the demographics of the patient included because doses to exposed individuals population (see Table 43), and time, distance, approach 1 millisievert (0.1 rem). However, and shielding factors, we estimate that the palladium 103 implants are not included because collective dose per procedure is 3 times the doses to exposed individuals are always less than maximal dose (i.e., the dose to the most exposed 1 millisievert (0.1 rem).
individual). 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 the following addition to the person receiving the maximal dose, manner. It was assumed that all patients would who is likely to be the primary care-provider, remain hospitalized until the dose dropped to there could be two other people who will average 1 millisievert (0.1 rem). Thus, the dose to the 21 NUREG-1492
i Table 4.9 Estimates of Collecthe Dose from Therapeutic Radiolodine Procedures for Alternative 1:
Annual Limit of 1 millislevert (0.1 rem) l Therapeutic Typical Activity Collective Estimated Total Procedure Administered Dose / Procedure Procedures Collective Dose 3
(radionuclide)
(MBq) (mCl)
(mSv)
(rem) per Year (person-Sv (rem))
Thyroid Ablation
- iodine-131 1,110 (30) 3.0 (03) 49,000 147 (14,700) 2,220 (60)*
3.0 (03) 1,000 3
(300) i Thyroid Cancer iodine-131 5,550 (150) 3.0 (03) 10,000 30 (3,000) l Permanent implant f
- iodine-125 1,480 (40) 2.2 (0.22) 2,000 4.4 (440)
All Therapeutic Procedures 62,000 184.4 (18,440)
- Maximum activity administered. ' Itis 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.
t j
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 Therapeutic Typical Activity Collective Estimated Total Procedure Administered Dose / Procedure Procedures Collective Dose (radionuclide)
(MBq) (mCl)
(mSv)
(rem) per Year (person-Sy (rem))
l Thyroid Ablation iodine-131 1,110 (30) 5.2 (0.52) 49,000 255 (25,500) 2,220 (60)*
9.0 (0.9) 1,000 9
(900)
Thyroid Cancer
- iodine-131 5,550 (150) 3.0 (03) 10,000 30 (3,000) l Permanent implant
- iodine-125 1,480 (40) 2.2 (0.22) 2,000 4.4 (440)
All Therapeutic Procedures 62,000 298.4 (29,840)
- Maximum activity administered. This analysis assumes that 98 percent of the patients are typically administered j
1,110 millisieverts (30 millicuries) and that 2 percent are administered the maximum quantity.
NUREG-1492 22
l Table 4.11 Estimates of Collective Dose from Therapeutic Radiolodine Procedures for Alternative 3:
Annual Limit of 5 millisleverts (0.5 rem)
Therapeutic Typical Activity Collective Estimated Total Procedure Administered Dose / Procedure Procedures Collective Dose (radionuclide)
(MBq) (mCl)
(mSv)
(rem) per Year (person Sv (rem))
Thyroid Ablation
- iodine-131 1,110 (30) 5.2 (0.52) 49,000 255 (25,500) 2,220 (60)*
10.4 (1.04) 1,000 10.4 (1,040)
Thyroid Cancer
- iodine-131 5,550 (150) 5.6 (0.56) 10,000 56 (5,600)
Permanent Implant
- iodine-125 1,480 (40) 2.2 (0.22)
.!,000 4.4 (440)
All Therapeutic Procedures 62,000
^
325.8 (32,580)
- Maximum activity administered. This 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.
most exposed individual is 1 millisievert (0.1 rem).
is 3 millisieverts (03 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 1 day of hospitalization to allow the typical and maximum quantities of iodine-131 for retained activity to reach the release limit. Upon a
thyroid ablation require about 7 and 14 days of release, the estimated dose to the maximally j
hospitalization, respectively, before release can be exposed individual is 1 millislevert (0.1 rem).
authorized. Whereas, thyroid cancer patients Therefore, the collective dose is 3 millisieverts administered the typical quantity of iodine-131 (03 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 the following collective dose per procedure was determined in manner. For thyroid ablations using the typical the following 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 megabecquerels (30 millicuries). The dose from each activity is less than 5 millisieverts collective dose is 3 times the individual dose (i.e.,
(0.5 rem). The individual doses from the typical 1,73 millisieverts (0.173 rem)) or 5.2 millisieverts and maximum activities are 1.73 millisieverts (0.52 rem). On the other hand, patients (0.173 rem) and 3.47 millisieverts (0.347 rem),
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 the maximum from these patients will be greater than the dose activity. The collective dose per procedure for from a patient administered 1,110 megabecquerels iodine-125 implants was calculated in the same (30 millicuries) due to biological considerations.
manner assuming no hospitalization. For thyroid The estimated dose to the most exposed individual cancer, administrations of 5,500 megabecquerels 23 NUREG-1492
l (150 millicuries) require no hospitalization In the analysis that follows, these costs are because the dose to the maximally exposed calculated assuming that all retained patients will individual is 1.86 millisieverts (0.186 rem). The be hospitalized. While retention costs might be collective dose is 5.6 millisleverts (0.56 rem).
less for non-hospital locations, no attempt is made in this analysis to quantify the potential costs.
4.2.5.2 Collective Dose to Breast 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-sievert (0.1 rem) by giving the woman instructions Durations of Patient Retention 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 Feeding Infants). The actual doses that would be patients would need to remain under licensee received by most infants after mterruption should control for each alternative were discussed in be a small fraction of 1 milhsievert (0.1 rem) or Section 4.2.5.1 Collective Dose to Individuals.
noth, g m the case of cessation. Consequently' m
Table 4.12 summarizes the duration of retention 1
there is no reason to calculate the collective dose per therapeutic procedure, to nurstng mfants from breast-feedmg smce it does not affect the choice of alternative.
Cost of Patient Retention T estimate the annual dollar costs for these 4.3 Value Impact Analysis periods of retention, one needs only multiply the number of days required for each procedure by 4.3.1 Estimates of the Potential Costs the number of procedures per year and the average cost per day of hospitalization. In 1990, The analysis in Section 4.2 indicates that the the average cost per day in a community hospital i
1 millisievert (0.1 rem) per year dose limit was $687 (SA92). The per diem cost at the imposed by Alternative 1 would result in the beginmng of 1995 is estimated to be $800, i
smallest collective dose to individuals exposed to However, as the current regulations require that released patients. The benefit of smaller doses patients who are hospitalized due to a therapeutic estimated for Alternative 1 will only be achieved if administration of radiopharmaceuticals be placed the patients to whom the radioactive materials in a private room, the $800 per day esumate is have been administered are retained under the adjusted to $1,000 per day. Using this figure, the J
control of licensees for longer periods of time.
Potential cost of retaining patients under The impact of retaining patients must be assessed Alternative 1 is estimated to be $427 million.
in terms of the patient, family, and society as a Under Alternative 2, the estimated cost is whole. At a minimum, the economic cost must
$16 million. And, under Alternative 3, there is no consider the direct cost of medical resources related cost because hospitalization is not required to retain the patient in a hospital and the required.
indirect cost resulting from the loss of human resources. Additional consideration should be Estimates of the Numbers of Breast Feeding given to the psychologicalimpact of retention on Women Requiring Records and Instructions j
the affected individual and family members.
Under Alternative 3 i
Hospitalization will also cause an increase in the dose to the hospital staff and other patients in the The rule associated with Alternative 3 establishes hospital. However, the increase in dose to the additional requirements for recordkeeping and hospital staff is expected to be low relative to a providing instructions. Before one can determine patient going home earlier because of the the costs of these requirements, it is necessary to precautions taken during hospitalization; calculate the number of patient releases involving e.g., patients are isolated and the hospital staff breast-feeding women that apply to each rarely enters the patient's room.
requirement.
NUREG-1492 24 j
Table 4.12 Duration of Retention per Therapeutic Procedure i
Alternative 1 Alternative 2 Alternative 3 (days)
(days)
(days)
Typical Activity hospital total hospital total I
'Iherapeutic Administered days per hospital days per hospital days per procedures Procedure (MBq) (mCl) procedure days procedure days procedure (x 1000)
Thyroid Ablation I-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 5,550 (150) 1.5 70,000 1.5t 15,000 0
0 Permanent Implant, I-125, 2,000 procedures / year 1,480 (40) 0 0
0 0
0 0
Total for All Therapeutic 427,000 16,000 0
Procedures
- Maximum activity administered. This analysis assumes that 98 percent of the patients are typically administered 1,110 millisieverts (30 millicuries) and that 2 percent are administered the maximum activity.
' The analysis under Section 4.2.5.1 Collective Dose to Individuals shows 1 day of hospitalization. However, patients are typically hospitalized for 1 to 2 days. 'Ihus, the actual observed value is shown.
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 j
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.S. For radiopharmaceuticals not cost of $0.6 million per year. In both cases, a cost i
identified in Table 4.2 but listed in Table B.5, the of $22 per patient is estimated. R atal i
number of administrations was assumed to be estimated cost ofinstructions is $2 m iion per year, 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 j
that 5 percent of them, based on information in Alternatives 1 and 2 have no recordkeeping i
Statistica: Abstracts of the United States (SA94),
requirements, and therefore, have no related j
could be breast-feeding (assuming an average costs. However, the rule 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 J
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 Gele 839, " Release of 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.
radiopharmaceuticals resulting 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 dose 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) the data in Table 4.2 were 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 j
As discussed above,13.5 percent of the 17,200 procedures per year would be subject to i
radiopharmaceuticals are administered to females these requirements (i.e., (1) 10,000 patients of childbearing age and 5 percent of them could treated with iodine for thyroid cancer and i
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.
j multiply 1.06 million by 13.5 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 Derivation of Indinct 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 However, the rule associated with Alternative 3 -
output lost or forfeited by the patient while NUREG 1492 26
Table 4.13 Annual Attributes of Alternatives 1,2, and 3 Cost Estimates Hospitalization Value of Records &
Hospital cost lost time Instructions Psychological Collective Dose Retention cost Alternative (person-rem)
(days)
(millions)
(millions)
(millions)
(relative) 1 18,400 427,000 427 15.62 0
High 2
29,840 16,000 16 0 96 0
Moderate 3
32,580 0
0 0
2.3 Low 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 iodine-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 normal life-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 (GNP). The GNP is considered the most While some of these elements of psychological comprehensive measure of the country's ecoromic costs are the result of the disease itself, others activity and includes the ruarket value of all goods such as disruption of normal routines, social l
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
$5,600 billion in 1991, the gross average annual related to patient retention. The conversion of per capita income of about $22,000 is derived.
psychological cost from patient retention to The value of $22,000 per year corresponds to equivalent dollars is complex such that an
$60 per day. To estimate the equivalent dollar evaluation is highly subjective and dependent upon value for the number of days lost due to retention the individual situation. Instead, this analysis uses of an individual for a therapeutic procedure, one a qualitative and reasonable approach to scope 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 43.13 Evaluation of Psychological Costs Retention of patients in a hospital by design Table 4.13 summarizes the data pertaining to the necessitates that the patient be " isolated" and that annual attriistes for each of the three alternatives human contact, inclusive of family members, is under consideration. To determine the preferred either avoided or minimized. Such isolation may alternative, the costs and benefits that result when bring about numerous changes and impositions in Alternatives 1 and 3 are each compared with the lives of the patient and family members that Alternative 2 (the status quo) were analyzed. The may in part be linked to, but are not reflected in, results are shown in Table 4.14. A value of $2,000 27 NUREG-1492
1 l
Table 4.14 Annual Costs and Benefits of Alternatives 1 and 3 Compared to Alternative 2
('Ibe Status Quo)
Collective Dose
- Costs Associated Hospitalization, Lost Time, Value Records and Instructions Net Benefit Dose Averted Alternative (person-rem)
(millions)
(millions)
(millions) 1 11,440 (savings) 23 (savings) 435 (cost)
-412 (net cost) 2 0
0 0
0 3
-2,740 (cost)
-5 (cost)
-14 (savings) 9 (net savings) l
- A value of $2,000 per person-rem was used as the conversion factor for dose averted.
j per person-rem was used as the conversion factor to radiation is not expected to result in doses
{
for dose averted (NRC95).
above 1 millisievert (0.1 rem) for long periods of 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 expressed the International Commission on Radiological by NRC, NCRP, and ICRP (see Section 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 Radiological Protection"; and the recommendations of the NCRP in NCRP Report 2.
Alternative 1 is considerably more expensive No.116, " Limitation of Exposure to Ionizing 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 dollar 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.
NUREG-1492 28
-. ~ ---
3.
Ahernative 3 relative to Alternative 2 has a.
administered to a patient, it may be possible.
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 Alternative 3 has psychological benefits to potential for repeated exposures to hospital 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 with Alternative 2.
provide physicians with the llexibility to not have to fractionate doses to avoid
- 4.. Basing the patient release criteria in hospitalization to meet the current 10 CFR 35.75 on the dose to individuals requirements, which may lead to a more exposed to a patient provides a consistent,.
effective treatment.
scientific basis for such decisions that treats all radionuclides on a risk-equivalent basis.
6.
Shorter hospital stays provide emotional 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 (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 be effective health care, appropriate for iodine-131, they are too high for some other radionuclides and too low for others.
6 IMPLEMENTATION 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 ocasional 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 millicuries) or less of iodine-131 are now may be released from their control.
I 29 NUREG-1492
d 7 REFERENCES ACR82 American College of Radiology, BU70 Buchan R.C.T. and J.M. Brindle,
" Manpower !!!: A Report of the 1970, "Radiciodine Therapy to Out-ACR Committee on Manpower,"
patients - The Contamination Chicago, IL.
Hazard," Br. J. Radiol 43:479.
ACR75 American College of Radiology, CA88 Carey, P.O., M.C. Lippert, W.C.
" Survey on Regionalization in Constable, D. Jones, B.M. Talton, 7
Nuclear Medicine," Washington, DC.
1988, " Combined Cold Seed Implantation and External ACS93 American Cancer Society, " Cancer Radiotherapy for Stage-B2 or C Facts & Figures 1992," Atlanta, GA.
Prostate Cancer," J. Urol. 139:989.
AG92 Agbi, C.B., M. Bernstein, N.
CA87 Carlton, C.E. and P.T. Scardino, Laperriere, P. Leung, M. Lumley, 1987, " Combined Interstitial and 1992," Patterns of Recurrence of External Irradiation for Prostatic Malignant Astrocytoma following Cancer," Prog. Clin. Biol. Res.
Stereotactic Interstitial 243B:141.
Brachytherapy with Iodine-125 Implants," Int. J. Radiat. Oncol. Biol.
CH80 Cheung, A., A.A. Driedger,1980, Phys. 23(2):321.
" Evaluation of Radioactive Phosphorus in the Palliation of Bl.88 Blake, G.M., M.A. Zivanovic, R.M.
Metastatic Bone Lesions from Blaquiere, D.R. Fine, AJ. McEwan, Carcinoma of the Breast and l
D.M. Ackery,1988, " Strontium-89 Prostate," Radiology 134:209.
Therapy; Measurement of Absorbed Dose to Skeletal Metastases,"
CL89 Clarke, D.H., G.K. Edmundson, J. Nucl. Med. 29:549.
A. Martinez, R.C. Matter, F. Vicini, E. Sebastian,1989, "The Clinical BL87 Blake, G.M., M.A. Zivanovic, Advantages of I-125 Seeds as a AJ. McEwan, B.R. Condon, D.M.
Substitute for Ir-192 Seeds in Ackery,1987, " Strontium-89 Temporary Plastic Tube Implants,"
Therapy: Strontium Kinetics and Int. J. Radiat. Oncol. Biol. Phys.
Dosimetry in Two Patients Treated 17(4):859, for Metastasizing Osteosarcoma," Br.
J. Radiol. 60:253.
CO87 Cobb, L.M. and S.A. Butler,1987,
" Treatment of the Murine BL71 Blum, M., R. Chandra, C.H.
Lymphoma A31 with Intravenous, Marshall,1971, " Environmental Sterilized "*"In-loaded A31 Cells,"
Contamination with 131-iodine Radiother. Oncol.10:217.
Related to the Treatment of Hyperthyroidism and Carcinoma of DE86 Delaney, T.F., W.U. Shipley, M.P.
the Thyroid Gland," IEEE Trans.
O' Leary, PJ, Biggs, G.R. Prout, Jr.,
Nucl. Sci., Ns-18(1):57.
1986, " Preoperative Irradiation Lymphadenectomy and I-125 BU71 Buchan R.C.T. and J.M. Brindle, implantation for Patient with 1971, "Radioiodine Therapy to Out.
Localized Carcinoma of the patients - The Radiation Hazard,"
Prostate," Int. J. Radiat. Oncol. Biol.
Br. J. Radiol. 44:973.
Phys.12:1779 NUREG-1492 30
~HE88 Herba, MJ., F.F. Illescas, M.P.
DG79 DeGroot,' LJ.,1979, "The Thyroid,"
In:. Textbook of Medicine, P.B.
Thirlwell, GJ. Boos, L, Rosenthall, 4
Beeson, W. McDermott, J.B.
M. Atri, P.M. Bret,1988, " Hepatic LWyngaarden, Eds., W.B. Saunders Malignancies: Improved Treatment
" Company, Philadelphia, PA; with Intraarterial Y-90," Radiology
'169:311.
EH87 Ehrhardt, GJ. and D.E. Day,1987,
" Therapeutic Use of Y 90 HE82 Herr, H.,1982, "PeMc j
Microspheres," Nucl. Med. Biol.
Lymphadenectomy and Iodine-125 14:233.
i Implantation in Genitourinary l
FDA85 Food and Drug Administration, Pr c es a d S gical Techniques, j
" Radiation Experience Data (RED),
D.E. Johnson, M.A. Boileau, Eds.,
1980, Survey of U.S. Hospitals,"
Duluth, MN, Grune and Stratton,63.
Department of Health, Education
~
and Welfare, Publication FDA 86-8253.
ICRP89 International Commission on i
Radiological Protection,1989, " Age-i FI89 Finkler, NJ., A.L Kassis, M.G.
dependent Doses to Members of the Muto, K. Weadock, S.S. Tumeh, Public from Intake of Radionuclides:
V.R. Zurawski, Jr., R.C. Knapp, Part 1," ICRP Publication No. 56, 1989, " Intraperitoneal Pergamon Press, Oxford, UK.
1 Radioiodinated OC 125 in Patients with Advanced Ovarian Cancer:
ICRP87 International Commission on Phase i Study," J. Nucl. Med. 30:904.
Radiological Protection,1987, e
" Radiation Dose to Patients from FL92 Fleischman, E.H., A.R. Kagan, O.E.
Radiopharmaceuticals," ICRP Streeter, J. Tyrell, M. Wollin, C.A.
Publication No. 53, Pergamon Press, Leagre, J.C. Harvey,1992, Oxford, UK.
" Iodine-125 Interstitial Brachy-therapy in the Treatment of Carcinoma 1'
ICRP78
' International Commission on of the Lung," J. Surg. Oncol. 49(1) 25.
Radiological Protection,1978, FR88 Fritjofsson, A., DJ. Cederlund, BJ,
" Limits for Intakes of Radionuclides i
Norlen, H. Wicklund,1988, by Workers," ICRP Publication
" Combined Therapy with Interstitial.
No. 30, Part 1, Pergamon Press, Gold Implantation and External Oxford, UK.
Irradiation in the Management of l
Prostate Cancer," Scand. J. Urol.
JA81 Jackson, G.L. and N. M. Blosser,
. Nephrol. Suppl. 110:117.
1981, " Intracavitary Chromic i
Phosphate (P-32) Colloidal Sus-
' FU91 Fuks, A., S.A. Lerbel, K.E. Wallner, pension Therapy," Cancer 48:25986.
C.B. Begg, W.R. Fair, L.L.
' Anderson,1991, "The affect of JA78 Jacobson, A.P., P.A. Plato, Local Control on Metastatic D. Toeroek,1978, "Contam, ation of m,
Carcinoma of the Prostate: Long
,[
Term Results in Patients Treated the Home Environment by Patients with I-125," Int. J. Radiat. Oncol.
Treated with Iodine 131," Am. J.
Biol. Phys. 21:537.
Public Health 68(3):225.
4 HA74 '
Harbert, J.C. and S. N. Wells,1974, JO83 Johnson, J.L and D.L. Abernathy,
" Radiation Exposure to the Family 1983, " Diagnostic Imaging Procedure of Radioactive Patients," J. Nucl.
Volume in the U.S.," Radiclogy 4
Med.15(10):887.
146:851.
31 NUREG-1492 i
.---~
i JOH83 Johns, H.E. and J.R. Cunningham, MA78 Martini, N., A.H. Freiman, R.C.
1983,"The Physics of Radiology,"
Watson, B.S. Hilaris,1978, " Intra-
. Fourth Edition, Charles C. Thomas pericardialInstillation of Radioactive
' Publisher, Springfield, IL Chromic Phosphate in Malignant Pericardial Effusion," AJR 128:639.
KA81 Kaplan, W.D., R.E. Zimmerman,
~
W.D. Bloomer, R.C. Knapp, SJ.
MA73 Marshall C.H., R. Chandra, Adelstein,1981, " Therapeutic M. Blum,1973, " Contamination of Intraperitoneal P-32: A Clinical Air and Surroundings by Patients Assessment of the Dynamics of Treated with Large Quantities of Distribution," Radiology 138:683.
I dine-131 for Thyroid Carcinoma,"
i CONF-730907 Part II, W.S. Snyder, Ed.,1169.
KE87 Ketring, A.R.,1987, " "Sm-EDTMP and '"Re-HEDP as Bone ME90 Meigooni, A.S., S. Sabnis, R. Nath, Therapeutic Radiopharmaceuticals,"
Nucl. Med. Biol.14:223.
1990, " Dosimetry of Palladium 103 Brachytherapy Sources for Perma-nent Implants," Endocurietherapy
[
KL87 Kloiber, R., C.P. Molnar, M. Barnes, Hyperthermia Oncology 6:107.
1987, "St-89 Therapy for Metastatic j
Bone Disease: Scintigraphic and ME86 Mettler, F.A. Jr., J.H. Christie, Radiographic Follow Up," Radiology A.G. Wi1 Hams, R.D. Moseley, CA.
)
163:719.
Kelsey,1986, " Population Charac-1 I
teristics and Absorbed Dose to the KO75 Kohler, G. and C. Milstein,1975, Population from Nuclear Medicine:
" Continuous Cultures of Fused Cells United States - 1982," Health Physics j
Secreting Antibody of Predefined 50(5):619.
Specificity," Nature 256:495.
ME85 Mettler, F.A. Jr., A.G. Williams, LA90 Lattimer, J.C., LA. Corwin, J.
J.H. Christie, R.D. Moseley, C.A.
Stapleton, WA. Volkert, GJ.
Kelsey,1985," Trends and Utilization f Nuclear Medicme m the United Ehrhardt, A.R. Ketring, S.K.
j Anderson, J. Simon, W.F.
States: 1972-1982," J. Nud. Med 26 20L i
Goeckeler,1990, " Clinical and M O92 Mohiuddin, M., F. Rosato, D.
Clinicopathologic Response of Anine l
Bone Tumor Patients to Treatment Barbot, A. Schuricht, W. Biermann, with Samarium-153-EDTMP," J.
R. Cantor, M hng4erm Resuks Nucl. Med. 31:1316.
f Comb,med Modality Treatment j
with I-125 Implantation for Car-cinoma of the Pancreas," Int. J.
LE85 Lenhard, R.E., S.E. Order, JJ.
Radiat. Oncol. Biol. Phys. 23(2):305.
Spunberg, S.O. Asbell, S.S. Leibel, j
1985, " Isotopic Immunoglobulin:
M O88 Morton, J.D. and R.E. Peschel, j
A New Systemic Therapy for 1988, " Iodine-125 Implants versus Advanced Hodgkin's Disease," J.
External Beam Therapy for Stage-l Clin. Oncol. 3:1296.
A2, B and C Prostate Cancer," Int.
J. Radiat. Oncol. Biol. Phys. 14:1153.
i MA88 Maxon, H.R., EA. Deutsch, S.R.
Thomas, K. Libson, SJ Lukes, C.C.
NCRP70 National Council on Radiation i
Williams, S. Ali,1988, "Re-186(Sn)
Protection and Measurements,1970 HEDP for Treatment of Multiple
" Precautions in the Management of Metastatic Foci in Bone: Human Patients who have Received Thera-Distribution and Dosimetric peutic' Amounts of Radionuclides,"
Studies," Radiology 166:501.
NCRP Report No. 37, Waslungton, DC.
+
NUREG 1401 32
NE90 Nelp, W.B., J.F. Eary, O.W. Press, PA84 Parker, T.L., F.A. Mettler, J.H.
C.C. Badger, PJ. Martin, F.R.
Christie, A.G. Williams,1984, Appelbaum, D. Fisher, B. Porter,
- Radionuclide Thyroid Studies: A I.E. Bernstein,1990, " Clinical Survey of Practice in the United Response and Toxicity Following States in 1981," Special Report, High Dose I 131 Antibody Treat-Radiology 150:547.
ment of Lymphoma," Eur. J. Nucl.
.Med.16:S124. ~
I
~
Pall Pasteau, O.,1911, "Traitment du cancer de la prostate par le NI80 Nishizawa, K., K. Ohara, M.
Radium," Rev. Mat. Nutt. 1911:363.
Ohshima, H. Mackoshi, T. Orito, T.
Watanabe,1980, " Monitoring of PE86 Pectasides, D., S. Stewart, N.
Iodine Excretions and Used Courtenay-Luck, R. Ramphng, AJ, Materials of Patients Treated with Munro, T. Krausz, B. Dhokia, D.
1-131," Health Physics 38(4):467.
Sn k, G. Hooker, H. Durbin, J.
Taylor-Papadimitriou, W.F. Bodmer, NRC97 U.S. Nuclear Regulatory Commission, A.A. Epenetos,1986, " Antibody.
Guided Irradiation of Malignant Regulatory Guide 8.39," Release of Pleural and Pericardial Effusions,"
Patients Administered Radioactive Br. J. Cancer 53:727.
Materials," Washington, DC,1997.
PE42 Pecher, C.,1942, " Biological Investi-NRC95 U.S. Nuclear Regulatory Commission,'
gations with Radioactive Calcium and November 1995, NUREG/BR-0058, Strontium: Preliminary Report on the Revision 2, " Regulatory Analysis of Use of Radioactive Strontium in the the U.S. Nuclear Regulatory Treatment of Metastatic Bone Cancer,"
Commission," Final Report,
' Univ. Calif. Pub. Pharmacol.11:117.
Washington, DC.
PO93 Porter, A.T. and J.D. Forman,1993, OR85 Order, S.E., G.B. Stillwagon,
" Prostate Brachytherapy. An Over.
J.L. Klein, P.K. Leichner, S.S.
view," Cancer 71 (3 Suppl):953.
Siegelman, E.K. Fischman, D.S.
Ettinger, T. Haulk, K. Kopher, PO90 Porter, A.T., J. Battista, D. Mason, l
K. Finney, M. Surdyke, S. Sels, R. Barnett,1990, "Ytterbmm-169; A i
S. Leibel,1985, " Iodine-131 Anti-Novel Pochytherapeutic Source,"
ferritine, A New Treatment Modality Clin. Invest. Med. Phys.13:198.
j in Hepatoma: A Radiation Therapy PR92 Priestly, J.B. Jr. and D.C. Beyer, Oncology Group Study," J. Clin.
Oncol. 3:1573.
1992, " Guided Brachytherapy for Treatment of Confined Prostate OS92 Ostertag, C.B. and F.W. Kreth,1992,
" Iodine-125 Interstitial Irradiation RI90 Riva, P., S. I amri, M. Agostini, G.
for Cerebral Gliomas," Acta Sarti, G. Moscatelli, G. Franceschi, Neurochi (Austria) 119(1-4):53, A. Spinelli, G. Vecchietti, R. Tassini, Freiburg University Federal D. Tirindelli,1990, " Intracavitary Republic of Germany.
Radioimmunotherapy Trails in Systemic Gastrointestinal and PA87 Park, C.H., J.H. Suh, H.S. Yoo, J.T.
Ovanan Carcinomas Pharmacokinetic, Lee, D.I. Kim, B.S. Kim,1987, Biologic and Dosimetric Problems,"
" Treatment of Hepatocellnlar Car-In: Schmidt HAE, Chambron J.,
cinoma (HCC) with Radiolabeled Eds., Nuclear Medicine -
Lipiodoh A Preliminary Report,"
Ouantitative Analysis in Imaging and Nucl. Med. Commun. 8:1075.
Function. Schattauer, Stuttgart, 586.
33 NUREG-1492
.. - ~
RO87 Robinson, R.G., J A. Spicer, D.F.
SI85 Silberstein, E.B., C. Williams,'1985, Preston, A.V. Wegst, N.L. Martin,
" Strontium-89 Therapy for the Pain 1987, " Treatment of Metastatic Bone of Osseous Metastases," J. Nucl.
Pain with Strontium-89," Nucl. Med.
Med. 26:345.
Biol.14:219. -
L RO77
- Roberts, DJ., 1977, "22P-sodium ST88 Stanbury, J.B.,1988, "The Physio-Phosphate Treatment of Metastatic logical Basis for Blockade of Radio-4 Malignant Disease," Clin. Nucl. Med.
iodine Retention by Iodine," in j
2:64.
Iodine Prophylaxis following Nuclear Accidents, Proceedings of a Joint
]
ROE 90 Roesler, H., J. Triller, L. Geiger, WHO/ CEC Workshop, E. Rubery H.U. Baer, H.P. Beer, L. Blumgart, and E. Smales, Eds., Pergamon 1990, Superselective 90Y resin Press, NY.
- 1 Embolization Therapy of Solid Tumors," Eur. J. Nucl. Med.16:439.
TU89 Turner, J.H., P.G. Claringbold, RU92 Rustig, S.N., S.S. Hahn,1992, E.L. Hetherington, P. Dorby, AA.
" Advantages of using High Activity Martindale,1989, "A Phase I Study I-125 Seeds in Temporary Interstitial of Samarium-153 Ethylenedia-Breast Implants," Med. Dosim.
minetetramethylene Phosphonate _
17(4):217.
Therapy for Disseminated Skeletal Metastases," J. Clin. Oncol. 7:1926.
- SA94 U.S. Bureau of the Census, 1
Statistical Abstract of the United States: 1994 (114th edition.)
WH88 Whitmore, W.F.,1988, " Interstitial
- Washington, DC.
Implantation of the Prostate:
10 Year Results, Brachytherapy SC92 Scharfen, C.O., P.K. Sneed, W.M.
Update,1988," In: Proceedings 'of i
Wara, DA. Larson, T.L Phillips, the Memorial Sloan Kettering M.D. Prados, KA. Weaver, M.
Cancer Center Course on Malec, P. Acord, K.R. Lamborn, Brachytherapy, B. Hilaris, Ed.
1992, "High Activity Iodine-125 Interstitial Implant for Gliomas," Int.
j J. Radiat. Oncol. Biol. Phys. 24(4):583.
ZI84 Ziessman, H A., J.H. Tleall, PJ.
i Yang, S.C. Walker, EA. Cozzi, J.E.
SC90 Schroder, LE., H.R. Maxon,1990, Niederhuber, J.W. Gyves, W.D.
"Re-186-HEDP Palliation of Painful Ensminger, M.C. Tuscan,1984, Skeletal Metastases," presented at
" Hepatic Arterial Perfusion the European Association of Nuclear Scintigraphy with Tc-99m MAA,"
Medicine Congress, Amsterdam.
Radiology 152:167.
4 NUREG-1492 34 1
.s
~
r
APPENDIX A j
PARAMETERS AND CALCULATIONS FOR DETERMINING RELEASE QUANTITIES AND DOSE RATES FOR RADIONUCLIDES USED IN MEDICINE Table A.1 Half Lives and Exposure Rate Constants of Radionuclides Used in Medicine
- 3 Exposure Exposure Half-Life Rate Constant Half-Life Rate Constant Radionuclide (days)
(R/mCl-h at 1 an)
Radionuclide (days)
(R/mCl h at I cm)
Ag-111 7.45 0.15 Pd-103 implant 16.%
1.48 *
- Au-198 2.696 23 Re-186 3.777 0.2 Cr-51 27.704 0.16 Re-188 0.708 0.26 Cu-64 0.529 1.2 Sc-47 3351 0.56 Cu-67 2 578 0.58 Se 75 119.8 2.6 Ga-67 3.261 0.753 Sm-153 1.946 0.425 I-123 0.55 1.61 Sn-117m 13.61 1.48 I-125 60.14 1.42 Sr-89 50.5 NAt I-125 implant 60.14 1.11' Tc-99m 0.251 0.756 I-131 8.04 2.2 TI201 3.044 0.447 In-111 2.83 3.21 Y-90 2.67 NAt Ir-192 implant 74.02 4.598 Yb-169 32.01 1.83 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 Ona@gy, Volume 6, April 1990. 'the exposure rate constant given is an " apparent" value (i.e., with respect to an apparent source activity) and takes into account the attenuation of gamma rays within the implant capsule itself.
8 R. Nath, A.S. Meigooni, and J.A. Meli, " Dosimetry on Transverse Axes of ml and p21r Interstitial Brachytherapy Sources,"
Medical Physics, 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 attenuation of gamma rays within the implant capsule itself.
' Not applicable (NA) because the release activity is not based on beta emissions.
NOTE: Although non-byproduct materials are not regulated by the NRC, information on non-byproduct material is included in this regulatory analysis for the convenience of the license.
A.1 NUREG-1492
Z Table A.2 Exposure Rate Constants, Release Activities, and Release Dose Rates'-
Clcm Release C
Release Activity Based On g
Linear Energy-Exposure Rate 0.5 rem to Total Decay Dose Rate 8
g Intensity Absorption at 1 Meter Half-Life" (fraction /
Energy 8 Coefficient 88 MeV/cm/
R/Ci-hr R/ mci-br Q
Q Q
for Q Isotope (days) disintegration) (MeV)
(1/m) disintegration at 1 Meter at I c m (mci)
(MBq)
(GBq)
(mrem /hr)
Ag-111 7.45 0.000245 0.022984 430E-02 2.42E-09 3.63E-05 3.63E-04 0.000462 0.023174 4.00E-02 4.28E-09 6.42E-05 6.42E-04 0.000151 0.0261 2.80E-02 1.10E-09 1.65E-05 1.65E-04 0.001202 0.09675 3.00E-03 3.49E-09 5.23E-05 5.23E-04 (Occupancy Factor = 0.25) 0.012291 0.24539 3.60E-03 1.09E-07 1.63E-03 1.63E-02 0.0668 0.34213 3.80E -03 8.68E-07 1.30E-02 130E-01 0.000559 0.65472 3.80E-03 139E-08 2.09E-04 2.09E-03 Exposure Rate Constant (Total)* 1.50E-02 1.50E-01 5.17E + 02 1.91E+ 04 1.91E +01 7.76E+ 00 Au-198 2.6 %
(Occupancy Factor = 0.25)
Exposure Rate Constant ** 2.30E-01 2.30E +00 932E +01 3.45E +03 3.45E + 00 2.14E +01 h
Cr-51 27.704 (Occupancy Factor = 0.25)
Exposure Rate Constant ** 1.60E-02 1.60E-01 130E + 02 4.82E + 03 4.82E + 00 2.09E +00 Cu-64 0.529 (Occupancy Factor = 1.0)
Exposure Rate Constant ** 1.20E-01 1.20E +00 2.28E +02 8.42E +03 8.42E + 00 2.73E + 01 Cu-67 2.578 (Occupancy Factor = 0.25)
Exposure Rate Constant
- 5.80E-02 5.80E-01 3.87E +02 1.43 E + 04 1.43E + 01 2.24E +01 Ga-67 3.261 0.02856 0.091266 3.00E-03 7.82E-08 1.17E-03 1.17E-02 0357 0.093311 2.95E-03 9.83E-07 1.47E-02 1.47E-01 0.19706 0.18458 3.40E-03 1.24E-06 1.85E-02 1.85E-01 0.02242 0.20895 3.50E-03 1.64E-07 2.46E -03 2.46E -02 (Occupancy Factor = 0.25) 0.15994 0 3 0022 3.75E-03 1.80E-06 2.70E-02 2.70E-01 0.044768 0 3 9353 3.90E-03 6.87E-07 1.03E-02 1.03E-01 0.001385 0.88769 3.65E-03 4.49E-08 6.73E-04 6.73E-03 O.001247 0.62941 3.85E-03 3.02E-08 4.53E-04 4.53E -03 Exposure Rate Constant (Total)* 7.53E-02 7.53E-01 235E+02 8.71E + 03 8.71E + 00 1.77E +01 2
Table A.2 Exposure Rate Constants, Release Activities, and Release Dose Rates (Continued)'
Linear Energy-Release Activity Based On Release Exposure Rate 0.5 rem to Total Decay h Rate Intensdy
- Absorption at 1 Meter IIalf-Life" (fraction /
Energy
- Coefficient **
MeV/cm/
R/Ci-br R/ mci-br Q
Q Q
for Q Isotope (days) disintegration) (MeV)
(1/m) disintegration at 1 Meter at I cm (MCI)
(MBq)
(GBq)
(mrem /hr) 1-123 0.55 (Occupancy Factor = 1.0)
Exposure Rate Constant
- 1.61E-01 1.61E + 00 1.63E + 02 6.04E +03 6.04E +00 2.63E + 01 I-125 60.14 0.39233 0.027202 2.60E-02 2.77E-06 4.16E-02 4.16E-01 0.73196 0.027472 2.50E-02 5.03E-06 7.54E-02 7.54E-01 (Occupancy Factor = 0.25) 0.25409 0.031 1.73E-02 I J6E-06 2.04E-02 2.04E-01 0.0649 0.035492 1.20E-02 2.76E-07 4.14E-03 4.14E-02 Exposure Rate Constant (Total)* 1.42E-01 1.42E +00 6.77E + 00 2.50E +02 2.50E-01 9.61E-01 I-131 8.04 (Cwey=Ky Factor = 0.25)
Exposure Rate Constant" 2.20E-01 2.20E +00 3.27E + 01 1.21E + 03 1.21E + 00 7.19E + 00 U
In-111 2.83 (Occupancy Factor = 0.25)
Exposure Rate Constant *** 3.21E-01 3.21E + 00 636E + 01 235E+03 235E + 00 2.04E + 01 fr-192 74.02 (Occc eKy Factor = 0.25) r Exposure Rate Constant" 4.80E-01 4.80E +00 1.63E+ 00 6.02E + 01 6.02E-02 7.81E-01 Pd-103 16.96 0.2866 0.02007 6.20E-02 3.57E-06 535E-02 535E-01 0.5443 0.02022 6.10E-02 6.71E-06 1.01E-01 1.01E +00 0.169 0.02272 6.00E-02 2J0E-06 3.45E-02 3.45E-01 (Occupancy Factor = 0.25) 0.00003 03524 3.80E-03 4.02E-10 6.02E-06 6.02E-05 0.00009 03975 3.90E-03 1.40E -09 2.09E-05 2.09E-04 0.000005 0.4971 3.90E-03 9.69E-11 1.45E-06 1.45E-05 Exposure Rate Constant (Total)* 1.89E-01 1.89E + 00 1.80E + 01 6.67E + 02 6.67E-01 3.41E + 00 ZCc (11 9x8
2 Table A.2 Exposure Rate Constants, Release Activities, and Release Dose Rates (Continued)'
C lc b
Release Release Activity Based On a
Linear Energy-Exposure Rate 0.5 rem to Total Decay Dose Rate I
Intensity
- Alnerption at 1 Meter llatf-Life" (fraction /
Energy
- Coefficient **
MeV/cm/
R/Ci-hr R/mCiar Q
Q.
Q for Q Isotope (days) disintegration) (MeV)
(1/m) disintegration at 1 Meter at I cm (mci)
(MBq)
(GBq)
(mrem /hr)
Re-186 3.777 (Occupancy Factor = 0.25)
Exposure Rate Constant"* 2.00E-02 2.00E-01 7.65E + 02 2.83E + 04 2.83E +01 1.53E +01 Re.188 0.708 (Occupancy Factor = 1.0)
Exposure Rate Constant"* 2.60E-02 2.60E-01 7.85E + 02 2.91 E + 04 2.91E + 01 2.04E +01 Sc-47 3351 (Occupancy Factor = 0.25)
Exposure Rate Constant" 5.60E-02 5.60E-01 3.08E + 02 1.14E + 04 1.14E + 01 1.72E + 01 So-75 119.8 (Occupancy Factor = 0.25)
Exposure Rate Constant" 2.00E-01 2.00E+ 00 2.41E + 00 8.92E +01 8.92E-02 4.82E-01 A
Sm-153 1.946 0.17263 0.040902 7.70E-03 5.44E-07 8.15E-03 8.15E-02 0 31218 0.041542 730E-03 9.47E-07 1.42E-02 1.42E-01 0.12217 0.047 4.60E- 03 2.64E-07 3.%E-03 3.%E-02 0.0517 0.069672 3.45E-03 1.24E-07 1.86E-03 1.86E-02 0.00194 0.075422 335E-03 4.90E-09 735E-05 7.35E-04 (Occupancy Factor = 0.25)
C.002 0.083366 3.20E-03 534E-09 8.00E-05 8.00E-04 0.00158 0.089484 3.00E-03 4.24E-09 636E-05 636E-04 0.00718 0.09743 3.00E-03 2.10E-08 3.15E-04 3.15E-03 0.283 0.10318 3.00E-03 8.76E-07 131E-02 1.31E-01 0.002775 0.42266 3.85E-03 4.52E-08 6.77E-04 6.77E-03 Exposure Rate Constant (Total)* 4.23E-02 4.25E-01 6.99E +02 2.59E + 04 2.59E + 01 2.97E +01 i
s Table A.2 Exposure Rate Constants, Release Activities, and Release Dose Rates (Continued)*
Release Release Activity Based On Linear Energy-Exposure Rate 0.5 rem to Total Decay Dose Rate Intensity
- Absorption at 1 Mcter Half-Life" (fraction /
Energy
- Coefficient **
MeV/cm/
R/Ci-hr R/ mci-hr Q
Q, Q
forQ.
Isotope (days) disintegration) (MeV)
(1/m) disintegration at 1 Meter at I cm (mci)
(MBq)
(GBq)
(mrem /hr)
Sa-117m 13.61 0.1873 0.025 335E-02 1.57E-06 235E-02 0351-01 03514 0.0253 330E-02 2.93E-06 4.40E-02
- 4. 6 6 - 01 0.1185 0.0285 2.25E-02 7.60E-07 1.14E-02 1 14E-01 (Occupancy Factor = 0.25) 0.0211 0.156 3.25E-03 1.07E-07 1.60E-03 1.60E-02 0.864 0.1586 330E-03 4.52E-06 6.78E-02 6.78E-01 Exposure Rate Constant (Total)*
1.48E-01 1.48E +00 2.87E + 01 1.06E +03 1.06E +00 4.25E + 00 Tc-99m 0.251 0.021021 0.018251 7.90E-02 3.03E-07 4.54E-03 4.54E-02 0.040194 0.018367 7.90E-02 5.83E-07 8.74E-03 8.74E-02 0.012059 0.0206 5.90E-02 1.47E-07 2.20E-03 2.20E-02 (Occupancy Factor = 1.0) 0.8907 0.14051 3.20E-03 4.00E-06 6.00E-02 6.00E-01 0.000214 0.14263 3.20E-03 9.77E-10 1.46E-05 1.46E-04 ta Exposure Rate Constant (Total)* 7.56E-02 7.56E-01 7.62E + 02 2.82E +04 2.82E + 01 5.76E +01 T1-201 3.044 0.0022 0.0306 1.80E-02 1.21E-08 1.82E-04 1.82E-03 0.27357 0.068895 3.45E-03 6.50E-07 9.75E-03 9.75E-02 0.46525 0.070819 3.40E-03 1.12E-06 1.68E-02 1.68E-01 0.20465 0.0803 3.20E-03 5.26E-07 7.88E-03 7.88E-02 (Occupancy Factor = 0.25) 0.0265 0.13534 3.20E-03 1.15E-07 1.72E-03 1.72E-02 0.0016 0.16588 330E-03 8.76E-09 131E-04 131E-03 0.1 0.16743 330E-03 5.53E-07 8.28E-03 8.28E-02 Exposure Rate Constant (Total)*
4.47E-02 4.47E-01 4.25E +02 1.57E +04 1.57E +01 1.90E + 01 2C;cm 9
I iS
2 Table A.2 Exposure Rate Constants, Release Activities, and Release Dose Rates (Continued)*
Clc b
Release Release Activity Based On
,L Linear Energy-Exposure Rate 0.5 rem to Total Decay Dose Rate y
latensity Absorption at 1 Meter 8
Half-Life" (fraction /
Energy 8 Coefficient "
MeV/cm/
R/Ci-hr R/ mci-hr Q,
Q, Q.
for Q.
Isotope (days) disintegration) (MeV)
(1/m) disintegration at 1 Meter at I cm (mci)
(MBq)
(GBq)
(mrem /hr)
Yb-169 32.01 0.002134 0.02075 6.00E-02 2.66E-08 3.98E-04 3.98E-03 0.52777 0.049773 5.25E-03 138E-06 2.07E-02 2.07E-01 0.93411 0.050742 5.05E-03 239E-06 3.59E-02 3.59E-01 038301 0.0575 4.25E-03 936E-07 1.40E-02 1.40E-01 0.43747 0.063119 3.75E-03 1.04E-06 1.55E-02 1.55E-01 0.026578 0.093613 3.05E-03 7.59E-08 1.14E-03 1.14E-02 0.17363 0.10978 3.05E-03 5.81E-07 8.72E-03 8.72E-02 0.018818 0.11819 3.10E-03 6.89E-08 1.03E-03 1.03E-02 (Occupancy Factor = 0.25) 0.11058 0.13052 3.20E-03 4.62E-07 6.92E-03 6.92E-02 0.21437 0.17721 3.40E-03 1.29E-06 1.94E-02 1.94E-01 03492 0.19795 3.60E-03 2.49E-06 3.73E-02 3.73E-01 0.001222 0.2403 3.60E-03 1.06E-08 1.59E-04 1.59E-03 0.017654 0.26107 3.65E-03 1.68E-07 2.52E-03 2.52E-02 h
0.10806 0 3 0773 3.75E-03 1.25E-06 1.87E-02 1.87E-01 0.001843 0 34406 3.80E-03 2.41 E-08 3.61E-04 3.61E-03 Exposure Rate Constant (Tutal)* 1.83E-01 1.83E + 00 9.87E + 00 3.65E +02 3.65E-01 1.81E +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. I1, Limiting Values of Radionuclide intake and Air Concentration and Dose Conversion Factors for Inhalatien, Submersion, and Ingestion," Report No. EPA-520/1-88-020 Office of Radiation Programs, U.S. Environmental Fratection Agency, Washington, DC,1988.
' Values for the intensity and energy for Ag-111, Ga-67,1-125, Sm-153. Tc-99m, T1-201, and Yb-169 were taken from: Bernard Shleien, 7he Heahh Physics and Radelogical Health Handbook, Revised Edition, Scinta, Inc.,1992, pees 294-334. For Sn-117m, the values for intensity and energy were taken from: L.M. Unger and D.K. Tmbey, " Specific Gamma-Ray Dose Cor.stants for Nuclides Important to Dosunetry and Radiological Assessment,* U.S.
Department of Energy, ORNL/RSIC-45/R1,1982. For Pd-103, the value? for inteanty and energy were taken: A.S. Meigooni and R. Nath, "A Comparision of Radial Dose Functions for "*Pd, s2sg, usSm, 2Am, '"Yb, "2Ir, and "Ce BrachytherapySources,"InternationalJournalofRaAarron Onmlogy-Bk:!ogy-Physics, Volume 22, Number 5,1992.
88 Values for the linear energy-absorption coefficient in air were taken from: Radiologeal Health Handbook, U.S. Department of Health, Education, and Welfare, page 135,1970.
~
~
.~..
. -.. ~
- ~ ~... -. ~.
,n-..
+ -
. ~... _
'* The' exposure rate constant was cak=Imaart because the published value for this isotope was an appronm* value, presented as a nage of values, or it varied -
from one reference to another. Only gamma rays and X-rays with energies above 113 kev were used to calculsee the exposure raec factor. The 113 kev cutoff is the one used in NCRP Report No. 41, " Specification of Gamma-Ray Brachytherapy Sources," 1974. The exposure rase constant was -4 ' f by using
[
the following equation:
li mRcm2 dis 1
A cni gm mR erg l
4 mci hr )( 4r (100 cm)2 ) 3 (5 (,g,.cm')( 87.6 erg)(1.6 x 10 MeV )
P (1332 x 10"-
=
4 mci hr i
Where 4 = the energy of the ith gamma ray or X-ray i, MeV.
f f; = the probabahty of decay (i.e., antensuty) of gamma rays or X-rays with energy 5 per Am*gration
.l m - the linear energy absorption
- in air of photons of energy E.
= the denssty of air at Waartmed temperature and pressure, taken to be 0.0012929 gm/enf.
p i
- R*A*gcol Health Nasdbook, U.S. Department of Heabh, Education, and Welfare,1970.
- D.E. Barber, J.W. Baum, and C.B. Meinhold, *Radiatnon Safety Issues Related to Radiolabeled Antibodies," NUREG/CR-4444, U.S. Nuclear Regulatory Conum===on, Washigton, DC,1991.
4 I
h I
i
[
l b
6 W
=
mO k
I r
-8 t
APPENDIX B PARAMETERS AND CALCULATIONS FOR DETERMINING INSTRUCTIONS TO PATIENTS WHO ARE BREAST-FEEDING
- l B.1 CALCULATIONAL already been made). Then, this maximum c ncentr tion w s assumed t ccur t 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br /> METHOD post admimstration. It might have been more conservative to extrapolate this back from the time at which the concentration was observed to The breast milk concentration of a 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, radiopharmaceutical as a function of time C(t),
nly ne Value was reported and a biological half-life was not available. If concentrations were (i.e., the activity per milliliter of breast milk) was calculated from the equation, rep rted 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 concentration reported was used without correction for biological removal, and assumed to C(t) = A a exp(-(A + A,)(t-3)),
(B.1) 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.
A computer program was written which used Equation B.1 describing breast milk concentration where A = the activity adm.. tered to the mis as a function of time represented by each scenario 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 A = 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 A, = physical decay constant, feeding (this represents a daily average consumption of 1,000 milliliters). Thus, the t = time at which breast-feeding occurs.
program calculated 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 j
was performed in early 1995. From the data excretion functions observed, multiplied by 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 r."i 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 u
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) i 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 /> j
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),
1 T were 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 u
Braast 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 />, literature were first corrected for radioactive the Grst calculation would have been for t = 24, decay to the time of administration (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 Inter,ial Dose Information Center (RIDIC), Oak Ridge Institute for Science and Education, Oak Ridge, TN.
B.1 NUREG-1492
- - -. -. - - - - - ~. -
i i
f uptake ofingested radiopharmaceuticals from the (MO89a). This is probably a conservative upper 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 was quickly and completely absorbed from the fraction of activity excreted in the breast milk over infant's GI tract.
the course of the study, the fraction of injected activity excreted per milliliter of milk at different Radi. tion doses for newborns (3.4 kg) and one-times was not available (although a clearance vor-olds (9.8 kg), based on the mathematical half life may have been reported). A single value phantoms of Cristy and Eckerman (CR87) have of cumulative excretion could not be used in this been estimated for the radiopharmaceuticals analysis, as it most likely represented the considered in this analysis and compiled in a cumulative fraction excreted assuming no
]
reference on pediatric radiation dosimetry in interruption of breast-feeding, and therefore could i
nuclear medicine (ST95). These dose estimates not be used directly to infer the cumulative generally apply to intravenous administration of fraction under different interruption schedules.
these pharmaceuticals. The dose estimates are To estimate the cumulative fraction under expressed as effective dose equivalents (EDE) per different interruption schedules, it was necessary
}
unit ingested activity; a summary of the values to calculate the time-dependent behavior of the used are given in Table B.1. (Some dose clearance. Thus, a breast milk concentration at
)
estimates, based on more recent models were early times was estimated which would result in a 1
supplied by the Radiation Internal Dose cumulative excretion equal to the value reported
)
Information Center, Oak Ridge, TN.) Typical assuming no interruption of breast-feeding, the values of activity administered to the woman per clearance half-life reported by the authors, and procedure were taken from various sources, to using the nursing schedule and volume assumed in estimate the total internal dose to the infant from this analysis. This derived early concentration was a typical procedure. There are certainly cases, then used in the computer program with the 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 should be considered.
None of the analyses for the iodine compounds included any considerations for free iodide in the The computer program estimated the intake and pharmaceutical product, while the other analyses subsequent dose to newborns and one-year-olds did not include considerations for possible for both the best and worst case scenarios, for no radioactive contaminants (except for the three interruption (firs'. feeding 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br /> after cases discussed below) or breakthrough products.
administration to Ae woman), and for the various These additional components of the dose are interruption schedules described above.
usually very small. Also, the assignment of numerical values to these quantities (the fraction An upper limit of 0.50 was placed on the total of tree iodide, percent activity of contaminants, fraction of administered activity which could be etc.) would be arbitrary, as these values vary excreted over all time in the breast milk. It was considerably between products, and even with possible for unrealistic values (e.g., fractions time.
greater than 1.0) to be calculated by merely permitting the computer program to sum the However, the presence of possible radioactive product of the fraction of activity per milliliter and contaminants in some of the pharmaceutical 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 excretion pathways available. This value is also contaminants in thallium 201 chloride. Finding compatible with the highest fraction reported for published information about the possible levels of total excretion of any radiopharmaceutical, namely these contaminants likely to be found in the a fraction of 033 for iodine-131 sodium iodide products was difficult. The most common source 1
NUREG 1492 B.2 '
L.
of these data is the radiopharmaceutical package the radiopharmaceuticalin breast milk as inserts. Discussion with some industry experts, descrbed abose (see Section B.1 CALCUIATIONAL however, indicated that the levels listed in most of METHOD). When data for a single subject were these inserts may considerably overestimate actual reported, the reported / derived value of excretion levels encountered in current practice. Therefore, fraction per milliliter of breast milk was the levels adopted for this analysis were those considered to be ' highest", for that publication, gathered as a consensus of son.e experts in and no " lowest
- value was listed. In some cases, measuring these quantities. The values used the breast milk peak concentration was estimated were: (1) indium 114m and indium-114 -
from graphical information in an article; these 0.25 percent, (2) iodine 125 0.01 percent, and estimates are shown with a "~" symbol.
(3) thallium 200 - 03 percent and thallium-202 -
1.2 percent. Although the additional dose from Robinson et al. (RO94) reported a concentration these contaminants is included in the values in and excretion half-life for a diagnostic dose of 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 irifant in that table reflects only the the iodine-131 administered in a therapeutic study.
contribution from the main radiopharmaceutical.
Murphy et al. (MU89) reported that thallium 201 chloride exhibited biphasic clearance. All other radiopharmaceuticals seemed to follow monophasic B.2 RESULTS clearance patterns, except for two case studies involving iodine-131 sodium iodide. This radiopharmaceutical was nonetheless modeled This analyses covers 25 of the radiopharmaceuticals wie a m n phasic clearance pattern for the most commonly used in nuclear medicine procedures purposes of this study.
involving women who are breast-feeding an infant.
Table B3 lists the biological and physical parameters used by the computer program to B.2.1 Biokinetic Data for Excretion calculate the total actisity ingested and the internal radiation doses received from the intake of Radiopharmacueticals in of radiopharmaceuticals in breast milk for Breast Milk newborns and one-year-olds.
The data obtained from the literature resiew are summarized in Table B.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 cumdative excretion fraction), and the worst case scenarios, and for all interruption reference. Most papers reported an effective schedules. Note, that in the case of iodine 131 r alf life for excretion of radiopharmaceuticals in sodium iodide the infant thyroid doses, instead of breast milk ind these values were com,rted to effective dose equivalents, were shown, due io the biological httf-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 it) and these of breast-feeding (which includes adjustment for values were used to estimate the concentrations of the external dose during breast feeding).
B3 NUREG-1492
Table B.1 Effective Dose Equivalents to Newborns and One-Year-Olds from Infant's Intake of Radiopharmaceuticals Effective Dose Equivalent * (rem /mCl)
Radiopharmaceutical Newborn One Year-Old j
Cr-51 EDTA 0.11 0.048 Ga-67 Citrate 6.7 2.6 I-123 mlBG" 5.9 4.1 1-123 0111 0.24 0.10 1123 Sodium lodide (Nal) 5.9 4.1 1-125 01H 0.89 036 I-131 0111 1.1 0.44 I-131 Sodium Iodide (Nal) 20,000' 14,000+
In-111 White Blood Cells 33 13 Tc 99m DISIDA 0.85 0.41 Tc-99m DTPA 0.13 0.056 Tc-99m DTPA Aerosol 0.28 0.12 i
Tc-99m Glucoheptonate 036 0.16 Tc-99m HAM 0.56 0.23 Tc-99m MAA 0.63 0.26 Tc-99m MAG 3 0.12 0.052 Tc-99m MDP 0.41 0.16 Tc-99m MIBI 0.52 0.24 Tc-99m 0 (Pertechnetate) 0.41 0.19 4
i Tc-99m PYP 0.28 0.12 l
1 Tc-99m RBC - In Vitro Labeling 031 0.14 Tc-99m RBC - In Vivo Labeling 030 0.14 Tc-99m Sulfur Colloid 0.74 036 Tc-99m White Blood Cells' O.41 0.19 TI 201 Chloride 15 8.5
- Effective dose equivalent to the infant per unit activity administered intravenously to the infant (except in the case of Tc-99m DTPA Aerosol).
" Specification tests indicated that the activity was most likely in the form of Na!, no_t mlBG. Thus, the dose estimate for I 123 mlBG is that shown for 1123 Nal.
' Dose to the infant's thyroid per unit activity administered intravenously (or orally) to the infant (rad / mci).
8 The values shown are actually the dose estimates for Tc-99m pertechnetste, as it was assume <l that activity released in breast milk from this product would be m the form of pertechnetate.
NUREG-1492 B.4
Table B.2 Excretloa Fractions and Biological Half-Uves for Radiopliarmaceuticals Excreted la Breast Milk Biological H alf U fe Measured for Excretion Fracticas*
Excretion Radiopharmiaceutical er T (br)
Refenace Cr 51 EDTA 1.5E-465 - 6.5E 465 5.0-7.0 AH85 Ga-67 Citrate 9.5E-5 (72) 216 TO76 2.7E-5 (38) - 3.7E-5 (58)82-385 RUM 5.6E-5 (%)
lA71 1.0E-4 (88)
GR83 43E-5 (48)
WE94 3.16E-256 - 9.9E-255 20-390 RU94 I 123 mIBG*
7.2E-6 (8) 85 KE94 I 123 OIH 6.0E-5 4.8 M O89b 1.2E-0256 - 3.5E-256 8.1 10.2 RO90 1.5E-4 (4) 83 RO90 I 123 Sodiun Iodide (Nal) 2.6E-265 10.4 HE86 6.5E-5 10.4 HE86 I-125 OJH 2.4E-256 4.8 AH85 I 131 OIH 1.8E-255 4.9E 266 2.2-6.0 AH85 I 131 Sodiun Iodide (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 RU88
~ 5.0E-4 13 RO94 (diag.)
11 RO94 (ther.
235 2 comp model) 23E-185 117 RU94 2.5E 166 - 4.6E 166 7.6-12 M O89a In 111 White Blood Cells 33E-7 (13)
(853)tt M O85 73E 7 (16)
(140)tt HE88 2.4E 7 (20)
BU86 Tc-99m DISIDA 1.0E-366 - 2.8E-366 10-(9.1)tt RU94 l
B.5 NUREG-1492
Table B.2 Excretion Fractions and Biological IIalf Lives for Radiopharmaceuticals Excreted i
in Breast Milk (Continued)
Biological IIalf-Life
{
Measured for
{
Excretion Fractions
- Excretion Radiopharmaceutical a
T. (hr)
Reference Tc-99m DTPA 7.2E-7 (2.2) 15 M O84$
6.0E 7 (2.8) 15 M085 5.0E-455 - 2.4E-355 6.5-30 RU94
~5.0E-7 (~3) 9.6 AH85 Tc-99m DTPA Aerosol Fraction of administered aerosol assumed to reach bloodstream (0.406) treated as Tc-99m DTPA.
Tc-99m Gluccheptonate 1.4E-355 9.0 RU94 2.6E-6 12 M O87 Tc-99m HAM 8.8E-356 - 1.1E-2il 6.0-(7.0)tt RU94 Tc-99m MAA 1.4E-4 (2.2) 20 M O84 7.1E-6 (5) - 3.1E-4 (7) 5.2-45 MA81 2.4E-5 (4) 53 BE73 1.4E-4 (3.5) 12 "
CR85 7.0E-6 (6)
~ 12 HE79 4.0E-355 - 5.2E-2il 7 3-18 AH85 Tc-99m 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 MIBI 1.4E-6 (33) 23 RU916 1.0E-455 - 3.0E-456 18-(6.7)tt RU94 Tc-99m 0, (Pertechnetate)
~6.7E-6 (8.5)
RU78 2.6E-5 (10) - 6.4E-5 (2) 9-66 WY73 1.4E-4 (22) 20 VA71
~ 13E-5 (3)
PI79 7.19E-3 (2.4) - 1.7E-2 (2)
OG83t
~5.0E-4 (~5) 6.9 AH85 1.7E-4 (8.2) 6 M O87 1.4E-4 (~3) 5.2 IIE86 Tc-99m PYP 1.5E-355 - 4.4E-365 8.4-(6.8)tt RU94 Tc-99m RBC -
2.0E-455 - 3.0E-455 (7.8-9.0)tt RU94 In Vitro Labeling NUREG-1492 B.6
Table B.2 Excretion Fractions and Biological llalf-Lives for Radiopharmaceuticals Excreted in Breast Milk (Continued)
Biological IIalf-Life Measured for Excretion Fractions
- Excretion Radiopharmaceutical T. (br)
Reference Tc-99m RBC -
6.0E-365 - 1.0E-265 (7.7)tt R O90 In Vivo Labeling 4.5E-5 (8)
(6.8)tt R O90
~ 1.0E-7 (~ 4)
(7)tt AH85 Tc-99m Sulphur Colloid 1.6E-366 - 1.5E-266 35-(8.3)tt RU94 Tc-99m White Blood Cells Treated as Tc-99m pertechnetate, as fraction of free Tc-99m is highly variable.
T1201 Chloride 2.2E-6 43 MU89 (2 com-1.9E-7 (362)tt partment model) 1.7E-6 13 3095 (2 com-9.5E-7 164 partment model)
Xe-133 Gas insignificant Dose to the breast-feeding infant.
- Peak fractirn per millibter of milk. All values corrected to the time of activity administration. The number in parenthesis la 'he time (b;) at which this maximum was observed, if data from more than one patient are reported, data are presented as a range.
- Pooled data from 4 patients.
t Patient admitted for study of enlarged thyroid,
- Conservatise value chosen due to anecdotal report (n=1) (see addendum of MOS4).
I 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.
tt 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 effective half-life was greater than the radionuclide's physical half-life (i.e., T, > T, indicates continued activity accumulation).
- Speciation tests indicated that the activity excreted was most likely in the form of Nal, po.t mlBG.
o B.7 NUREG-1492
Table B3 Biological and Physical Parameters Used to Calculate the Total Activity Ingested and Internal Radiation Doses Recched from the Intake of Radiopharmaceuticals in Breast Milk Biological Half Life Excretion Fraction
- for Excretion **
Administered Activity Lowest Ifighest Shortest Longest Radiopharmaceutical (mCl) a, a2 Tu (br)
Tu (hr)
Cr-51 EDTA 0.05 3.2E-7 1.4E-6 5
7 Ga-67 Citrate 5
8.0E-6 1.0E-4 20 390 1-123 mlBG 10 7.2E-6 7.2E-6 85 85 I-123 Olli 2
2.9E-5 1.5E-4 4.8 10.2 1-123 Sodium Iodide (Nal) 0.4 6.2E-5 6.5E-5 10.4 10.4 I-125 0111 0.01 7.1E-5 7.1E-5 4.8 4.8 I-131 OlH 03 43E-5 1.2E-4 2.2 6.0 I-131 Sodium lodide (Nal) 150 1.4E-5 6.7E-4 7.6 117 In-111 White Blood Cells 0.5 2.4E-7 73E-7 (85)
(140)
Tc-99m DISIDA 8
3.4E-6 4.6E-6 10 (9.1)
Tc-99m DTPA 20 5.0E-7 6.5E-6 6.5 30 Tc-99m DTPA Aerosol 1
2.0E-7 2.7E-6 6.5 30 Tc-99m Glucoheptonate 20 2.6E-6 4.9E 6 9
12 Tc-99m HAM 8
1.8E-5 23E-5 6
(7)
Tc-99m MAA 4
7.0E-6 3.1E-4 5.2 45 Tc-99m MAG 3 10 5.0E-7 6.5E-6 6.5 30 Tc-99m MDP 20 1.6E-6 1.6E-6 8.4 34 Tc-99m MIBl 30 2.2E-7 1.4E-6 18 (6.7)
Tc-99m 0, (Pertechnetate) 30 6.7E-6 1.7E-4 5.2 66 Tc-99m PYP 20 3.1E-6 9.2E-6 8.4 (6.8)
Tc-99m RBC In Vitro Labeling 20 33E-7 5.0E 7 (7.8)
(9)
Tc-99m RBC - In Vivo Labeling 20 1.0E-7 4.5E-5 (6.8)
(7) t l
NUREG-1492 B.8
Table H3 Hiological and Physical Parameters Used to Calculate the Total Activity Ingested and l
Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk (Continued)
Biological Hal'. Lib Excretion Fraction
- for Excretion **
Administered Activity Lowest liighest Shortest Longest Radiopharmaceutical (mCl) a, a2 T, (hr)
T,2 (hr)
Tc-99m Sulfur Colloid 12 2.8E-6 2.6E-5 35 (8.3)
Tc-99m White Blood Cells 30 6.7E-6 1,7E-4 5.2 66 TI-201 Chloride 3
1.7E-6 2.2E-6 13 43 9.5E-7 1.9E-7 43 (362)
- " Lowest" and " Highest" 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). These are combined with the shortest and longest biological half-hves for that radiopharmaceutical reported by any author. A given concentration and half-life combined to produce a supposedly best case or worst case scenario did not necessarily come from the name study.
- For some radiopharmacueticals, Tu and/or T,2 may be negative (i.e., values shown in parentheses) because these were the unusual cases reported in the literature in which the offective half-life was greater than the radionuclide's physical half-hfe (i.e., T, > T, indicates continued activity accumulation). In these cases, the effective half-life was used to perform the analysis.
4 B.9 NUREG-1492
Table B.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Hreast Milk Under Different Interruption Schedules Total Activity Effective Dose Equivalent Administered Interruption I"A Radio-Activity Time pharmaceutical (mCl)
Concentration (hr)
(mci)
(%)
Newborn 1-Yr-Old Cr-51 EDTA 0.05 minimum 3
7.71 E-06 1.54E-02 8.85 E-04 3.71 E-04 12 3.14E-06 6.27E -03 3.60E -04 1.51 E-04 24 9.44E-07 1.89E -03 1.08E-04 4.54E-05 48 8.55 E-08 1.71 E-04 9.81E-06 4.11 E -06 96 7.02E-10 1.40E-06 8.06E-08 3.38E-08 120 6.37E-11 1.27E-07 7.30E-09 3.06E-09 168 5.23E-13 1.05 E-09 6.00E-11 2.51E-11 336 1.56E-20 3.12E-17 1.79E - 18 7.50E - 19 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 maximum 3
3.37E-05 6.75E -02 3.87E-03 1.62E-03 12 1.37E-05 2.74E-02 1.57E -03 6.60E-04 24 4.13 E -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 6.15 E-06 3.53 E -07 1.48E -07 120 2.79E-10 5.57E -07 3.19E-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 Ga-67 Citrate 5
minimum 3
4.09E-02 8.17E -01 2.72E + 02 1.04E + 02 12 2.76E-02 5.52E-01 1.84E + 02 7.05 B + 01 24 1.64E -02 3.28E -01 1.09E + 02 4.18E + 01 48 5.77E -03 1.15 E-01 3.84E + 01 1.47E + 01 96 7.14E -04 1.43 E -02 4.76E + 00 1.82E + 00 120 2.51 E -04 5.03E-03 1.67E + 00 6.42E -01 168 3.11E-05 6.23E -04 2.07E-01 7.95 E-02 336 2.08E -08 4.17E-07 1.39E -04 5.32E-05 672 9.27E -15 1.85 E - 13 6.17E-11 2.37E-11 maximum 3
1.99E + 00 3.98E + 01 1.33E +04 5.08E + 03 12 1.81 E + 00 3.62E + 01 1.20E + 04 4.62E + 03 24 1.59E + 00 3.18E + 01 1.06E + 04 4.06E + 03 48 1.23 E + 00 2.47E + 01 8.21E + 03 3.15E + 03 96 7.40E -01 1.48E + 01 4.93 E + 03 1.89E + 03 120 5.73E-01 1.15 E + 01 3.82E + 03 1.46E + 03 168 3.44E-01 6.88E + 00 2.29E + 03 8.78E + 02 336 5.76E-02 1.15E + 00 3.83E + 02 1.47E + 02 672 1.61 E-03 3.23 E -02 1.07E + 01 4.12E + 00 NUREG 1492 B.10
1 l
Table B.4 Total Activity Ingested and Internal Radiation Doses Received from the intake of
)
Radlopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued) oalAc h Rec e u alent Administered Interruption In p ted (am m)
Radio.
Activity Time pharmaceutical (mci)
Concentration (br)
(MCI)
(%)
Newborn 1-Yr-Old I 123 m1BG*
10 n inimum 3
5.41E-02 5.41E-01 3.20E + 02 2.20E + 02 12 3.13E -02 3.13 E-01 1.86E + 02 1.28E + 02 24 1.51E-02 1.51 E-01 8.97E + 01 6.16E + 01 48 3.53 E-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 4.48E-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 5.41 E-01 3.20E + 02 2.20E + 02 12 3.13 E-02 3.13E-01 1.86E + 02 1.28E + 02 24 1.51 E-02 1.51 E-01 8.97E + 01 6.16E + 01 48 3.53 E-03 3.53 E -02 2.10E + 01 1.44E + 01 96 1.92E-04 1.92E-03 1.19E + 00 8.02E-01 120 4.48E-05 4.48E-04 3.04E-01 1.99E -01 168 2.44E-06 2.44E -05 4.01E-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 1-123 OIH*
2 minimum 3
1.63E-02 8.13 E-01 3.85E + 00 1.62E + 00 12 2.76E-03 1.38E-01 6.54E-01 2.76E-01 24 2.60E-04 1.30E- 02 6.17E -02 2.60E-02 48 2.31 E-06 1.15 E -04 5.49E-04 2.32E-04 96 1.82 E-10 9.08E-09 4.46E -08 1.89E-08 120 1.61 E-12 8.%E-11 4.32E -10 1.82E-10 168 8.79E-17 4.40E-15 6.84E
.4 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 maxmimum 3
1.24E -01 6.18E + 00 2.93 E + 01 1.24E + 01 12 4.18E-02 2.09E + 00 9.92E + 00 4.18E + 00 24 9.86E -03 4.93 E-01 2.33E + 00 9.865 E-01 48 5.48E-04 2.74E-02 1.31E-01 5.49E-02 96 1.69E-06 8.458 - 05 4.19E-04 1.77E-04 120 9.38E-08 4.69E-06 2.59E-05 1.09E-05 168 2.89E - 10 1.45E-08 2.09E-07 8.78E-08 336 0.00E + 00 0.00E + 00 1.43 E-12 6.00E-13 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00
- Includes the dose from radioactive contaminants. See Section B.1 CALCULATIONAL METHOD for details.
B.11 NUREG-1492
=
Table B.4 Total Activity Irgested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued)
- " ' ^
- Administered laterruption Ingested (mrem)
Radio-Activity Time pharmaceutical (mci)
Concentration (hr)
(mci)
(%)
Newborn 1 Yr-Old I-123 Nal*
0.4 minimum 3
1.038 - 02 2.58E 4 00 6.12E + 01 4.21E + 0!
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 48 4.84E-05 1.21E -02 2.89E-01 1.98 E-01 96 1.59E-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 0.00B + 00 0.00E + 00 5.08E-15 3.68E-15 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 maxmimum 3
1.08E-02 2.70E + 00 7.04E + 01 4.87E + 01 12 3.70E-03 9.252 - 01 2.83E + 01 1.98E + 01 24 8.86E-04 2.22E-01 1.17E + 01 8.27E + 00 48 5.08E-05 1.27E-02 6.74E + 00 4.87E + 00 96 1.67E-07 4.17E-05 6.44E + 00 4.66E + 00 120 9.56E-09 2.39E -06 6.44E + 00 4.66E + 00 168 3.14E -11 7.85E-09 6.44E + 00 4.66E + 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 1-125 OlH 0.01 minimum 3
2.52E-04 2.52E + 00 2.24E -01 9.04E -02 12 6.84E-05 6.84E-01 6.07E-02 2.45 E-02 24 1.20E-05 1.20E-01 1.07E-02 4.31E -03 48 3.72E-07 3.72E-03 3.30E-04 1.33 E-04 96 3.55E-10 3.55E-06 3.15 E-07 1.27E-07 120 1.10E-I l 1.10E-07 9.75E-09 3.94E-09 168 1.05E-14 1.05E-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 maxmimum 3
2.52E-04 2.52E + 00 2.24E-01 9.04E-02 12 6.848 - 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 3.55 E-06 3.15E-07 1.27E-07 120 1.10E-11 1.10E -07 9.75E-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 dose from radioactive contannants. See Section B.1 CALCULATIONAL METHOD for details.
f NUREG 1492 B.12
Table B.4 Total Activity Ingested and Internal Radiation Doses Recched from the Intake of
)
Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued)
- I ^** I
- * ** 9 " "'*"I Administered Interruption Ingsted (mrend Radio.
Activity Time pharmaceutical (mCl)
Concentration (hr)
(mci)
(%)
Newborn 1-Yr-Old I-131 O!H 0.3 minimum 3
2.62E-03 8.73E-01 2.91E + 00 1.16E + 00 12 1.49E-04 4.96E -02 1.65E -01 6.61 E 24 3.26E -06 1.09E-03 3.61E-03 1.45E-63 48 1.56E-09 5.19E -07 1.73E-06 6.91 E-17 96 3.48E-16 1.16E-13 3.86E-13 1.54E-- 13 120 0.00E + 00 0.00E + 00 0.00E + 00 0.00F +00 168 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
1.50E -02 4.998 + 00 1.66E + 01 6.65E + 00 12 5.13E-03 1.71E + 00 5.69E + 00 2.29E + 00 24 1.23 E-03 4.09E-01 1.36E + 00 5.45 E -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-%
168 4.38E-I l 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 0.00E + 00 0.00E + 00 1-131 Sodium lodide 150 minimum 3
1.06E + 00 7.07E-01 2.08 E + 07*
1.53 E + 07*
(Nal) 12 4.52E -01 3.01 E-01 8.86E + 06*
6.52 E + 06*
24 1.45 E-01 9.66E -02 2.84E + 06*
2.09E + 06*
48 1.49E-02 9.94E -03 2.92 E + 05
- 2.15E + 05*
96 1.58 E-04 1.05E-04 3.10E + 03*
2.28 E + 03
- 120 1.62E -05 1.08E -05 3.18 E + 02*
2.33 E + 02*
168 1.71 E-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*
maxmimum**
3 7.50E + 01 5.00E + 01 1.47E + 09*
1.08E + 09*
12 7.50E + 01 5.00E + 01 1.47E + 09*
1.08E + 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*
120 7.50E + 01 5.00E + 01 1.47E + 09*
1.08 E + 09
- 168 7.50E + 01 5.00E + 01 1.47E + 09*
1.08 E + 09
- 336 1.88E + 01 1.25 E + 01 3.69E + 08*
2.71 E + 08
- 672 7.68E-01 5.12E -01 1.51 E + 07*
1.11 E + 07*
- Dose to the infant thyroid, mrad.
" The values under Total Activity ingested and Effective Dose Equivalent for interruption 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 CALCULATIONAL METHOD).
l l
B.13 NUREG-1492
Table B.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk Under Different laterruption Schedules (Continued)
Total ActMty EMn be Quhalent Administered Interruption I "E***
I""")
Radio-Activity Time pharmaceutical (mci)
Concentration (hr)
(mci)
(%)
Newborn 1 Yr-Old in-111 0.5 minimum 3
6.21E-04 1.24E-01 3.53E + 01 1.32E + 01 White Blood Cells
- 12 5.77E-04 1.15E -01 3.29E + 01 1.23E + 01 24 5.23 E-04 1.05E-01 2.98E + 01 1.11E + 01 48 4.30E-04 8.60E-02 2.45E + 01 9.15E + 00 96 2.91 E-04 5.82E-02 1.66E + 01 6.19E + 00 120 2.39E-04 4.78E -02 1.36E + 01 5.09E + 00 168 1.62E-04 3.23E -02 9.21E + 00 3.44E + 00 336 4.11 E-05 8.22E-03 2.34B + 00 8.74E-01 672 2.66E-06 5.31E-04 1.51E-01 5.65E-02 maxmimum 3
3.10E-03 6.19E-01 1.76E + 02 6.59E + 01 12 2.96E-03 5.92E-01 1.69E + 02 6.29E + 01 24 2.79E-03 5.58E-01 1.59E + 02 5.93 E + 01 48 2.48E-03 4.95E-01 1.41 E + 02 5.27E + 01 96 1.95 E -03 3.91 E -01 1.11E + 02 4.16E + 01 120 1.73 E-03 3.47E-01 9.88E + 01 3.69E + 01 168 1.37E-03 2.74E-01 7.79E + 01 2.91 E + 01 336 5.95E-04 1.19E-01 3.39E + 01 1.27E + 01 672 1.13 E-04 2.26E-02 6.43E + 00 2.40E + 00 Tc-99m DISIDA 8
minimum 3
5.64E-03 9.99E-02 6.80E +00 3.25E + 00 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 1.68E-03 8.03E-04 96 1.97E-10 3.50E-09 2.38E -07 1.14E-07 120 2.358 - 12 4.16E-11 2.83 E-09 1.36E-09 168 3.21E-16 5.69E - 15 3.87E-13 1.85 E-13 336 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
2.25E-02 2.82E-01 1.92E + 01 9.17E + 00 12 1.13E-02 1.42E-01 9.66E + 00 4.62E + 00 24 4.55E-03 5.69E-02 3.87E + 00 1.85E +00 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 1.24 E -03 168 7.868 - 08 9.83 E-07 6.69E-05 3.20E-05 336 2.18E-13 2.73 B-12 1.86E-10 8.89E-11 672 0.00B + 00 0.00E + 00 0.00E + 00 0.00E + 00
- Includes the dose from radioactive contaminants. See Section B.1 CALCULATIONAL METHOD for details.
NUREG-1492 B.14
Table B.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued)
Administered Interruption Total Activity Effective Dose Equivalent Ingested (mrem)
Radio-Activity Time pharmaceutical (mci)
Concentration (br)
(mci)
(%)
Newborn 1-Yr-Old Tc-99m DTPA 20 minimum 3
2.57E-03 1.29E-02 3.23 E-01 1.43E-01 12 3.49E-04 1.74E-03 4.39E -02 1.94E-02 24 2.43E-05 1.22E-04 3.06E-03 1.35 E -03 48 1.18E-07 5.92E-07 1.49E-05 6.57E-06 96 2.80E-12 1.40E-11 3.52E -10 1.55 E -10 120 1.36E - 14 6.80E-14 1.71E-12 7.55E-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 maxmimum 3
4.78E-02 2.39E-01 6.02E + 00 2.65E + 00 12 1.38E-02 6.88 E-02 1.73 E + 00 7.64E-01 24 2.61E-03 1.31 E-02 3.29E-01 1.45E-01 48 9.43E-05 4.72E-04 1.19E -02 5.24E-03 96 1.23 E-07 6.14E-07 1.55 E-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 3.23E-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 Tc-99m DTPA 1
minimum 3
5.14E-05 5.14E-03 1.43 E-02 6.09E-03 Aerosol 12 6.98E-06 6.98E-04 1.94E -03 8.26E-04 24 4.87E-07 4.87E-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 + 00 maxmimum 3
9.93E-04 9.93 E-02 2.76E-01 1.18E-01 12 2.86E-04 2.86E-03 7.93 E-02 3.38E-02 24 5.43 E-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 2.55 E-09 2.55 E-07 7.08E-07 3.02E-07 120 9.21 E-11 9.21E-09 2.56E-08 1.098 - 08 168 1.20E-13 1.20E-11 3.33 E-11 1.42E-I l 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 672 0.00E + 00 0.00E + 00 0.00E t 00 0.00E + 00 B.15 NUREG-1492
Table B.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued) i ty Nye Nse Quhabt Administered Interruption IngestM (inrem)
Radio-Activity Time pharmaceutical (MCI)
Concentration (br)
(mci)
(%)
Newborn 1-Yr-Old Tc-99m 20 minimum 3
1.48E-02 7.41E-02 5.38E + 00 2.30E +00 Glucoheptonate 12 2.63E-03 1.31E -02 9.52E-01 4.08E-01 24 2.61 E-04 1.31E-03 9.48E-02 4.06E-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 l
120 2.51 E-12 1.25E-11 9.10E-10 3.90E-10 168 2.21E-16 1.11E-15 8.03E-14 3.44E-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 maxnumum 3
3.02E-02 1.51E -01 1.10E + 01 4.70E + 00 12 6.37E-03 3.19E-02 2.31E + 00 9.90E-01 24 7.99E-04 3.99E-03 2.908 -01 1.24E-01 48 1.25E-05 6.27E-05 4.55E-03 1.95E-03 96 3.10E-09 1.55 E-08 1.128 - 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-12 336 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 Tc-99m HAM 8
minimum 3
3.60E-02 4.50E-01 2.00E + 01 8.13 E + 00 12 4.51E-03 5.64E-02 2.50E + 00 1.02E + 00 24 2.83 E-04 3.54E-03 1.57E-01 6.38E-02 48 1.11E-06 1.39E-05 6.17E-04 2.51E-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 + 00 336 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 j
672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 maxmimum 3
8.95E-02 1.12E + 00 4.97E + 01 2.02E + 01 12 3.67E-02 4.59E-01 2.04E + 01 8.29E + 00 24 1.12E-02 1.40E-01 6.21E + 00 2.53 E + 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 8.35 E-07 1.04E-05 4.63E-04 1.88E-04 168 7.21E-09 9.01E-08 4.00E-06 1.63E-06 336 3.00E-16 3.75 E -15 1.66E-13 6.76E-14 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 NUREG-1492 B.16
i l
Table B.4 Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued)
" ^*
I Administered Interruption I"
Radio-Activity Time pharmaceutical (mci)
Concentration (hr)
(mci)
(%)
Newborn 1 Yr-Old Tc-99m M AA 4
minimum 3
6.66E-03 1.66E-01 4.19E + 00 1.70E + 00 12 7.11 E-04 1.78E-02 4.47E-01 1.81 E-01 24 3.60E-05 9.00E-04 2.26E-02 9.19E-03 48 9.23E -08 2.31E -06 5.81E-05 2.36E-05 96 6.07E-13 1.52E-l l 3.82E-10 1.55 E -10 120 1.54E -15 3.85E - 14 9.69E - 13 3.93E -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 maxmimum 3
4.78E-01 1.19E + 01 3.01 E + 02 1.22E +02 12 1.47E-01 3.68E + 0!
9.27E + 01 3.76E + 01 24 3.07E-02 7.68E-01 1.93E + 01 7.84 E + 00 48 1.33E-03 3.338 - 02 8.38E-01 3.40E-01 96 2.51E-06 6.28E-05 1.58E-03 6.41 E-04 120 1.09E-07 2.73 E -06 6.86E-05 2.78E -05 168 2.06E-10 5.14E -09 1.298 - 07 5.25E-08 336 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 Tc-99m MAG 3 10 minimum 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 7.25 E -I l 120 6.80E-15 6.80E-14 8.05 E -13 3.52E-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 maxmimum 3
2.39E-02 2.39E -01 2.83 E + 00 1.24E + 00 12 6.88E-03 6.88E-02 8.15E-01 3.56E-01 24 1.31E -03 1.31E-02 1.55E-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 1.15 E-07 168 2.89E-12 2.89E-11 3.42E-10 1.50E-10 336 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 B.17 NUREG-1492
Table B.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of i
Radiopharmaceuticals in Hreast Milk Under Diffennt Interruption Schedules (Continued)
Tota e ity Mecthe quivakat Administered Interruption Rads,o-Activity Time pharmaceutical (mCl)
Concentration (hr)
(mci)
(%)
Newborn 1-Yr-Old Tc-99m MDP 20 minimum 3
8.94E-03 4.47E-02 3.64E + 00 1.39E +00 12 1.51 E-03 7.53 E -03 6.13 B-01 2.34E-01 24 1.40E-04 7.02E-04 5.71E-02 2.18E-02 48 1.22E-06 6.09E-06 4.95 E-04 1.89E-04 96 9.16E-11 4.58E - 10 3.73E-08 1.42E-08 120 7.948 - 13 3.97E-12 3.23 E-10 1.23E-10 168 4.15E-17 2.08E-16 1.69E-14 6.45 E-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
1.20E-02 5.98E-02 4.87E + 00 1.86E + 00 12 3.53E-03 1.76E-02 1.44E + 00 5.48E-01 24 '
6.92E -04 3.46E-03 2.82E-01 1.08E-01 48 2.67E-05 1.33 E-04 1.09E-02 4.14E-03 96 3.96B-08 1.98E-07 1.61E-05 6.15 E-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 Tc-99m MIBl 30 minimum 3
2.23 E -03 7.44E-03 1.16E +00 5.37E-01 12 5.59E-04 1.868 - 03 2.90E-01 1.34E-01 24 8.83 E-05 2.948 - 04 4.57E-02 2.12E-02 48 2.20E-06 7.34E-06 1.14E-03 5.30E-04 95 1.37E-09 4.56E-09 7.098 - 07 3.29B-07 120 3.41E-11 1.14E-10 1.77E-08 8.21E-09 168 2.12E-14 7.08E-14 1.10E-11 5.11E - 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 maxmien.:n 3
1.97E-02 6.56E-02 1.02 E + 01 4.73E + 00 12 7.76E-03 2.59E -02 4.02E + 00 1.87E + 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 1.31 E-06 4.368 -06 6.77E-04 3.14E-04 120 1.09E-07 3.64E-07 5.66E-05 2.63 E-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
NUREG-1492 B.18
l
\\
Table B.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued)
Administered Interruption AcMty Ekthe Nse E@alent IngatM (mrem)
Radio-Activity Time pharmaceutical (mCl)
Concentration (hr)
(mCl)
(%)
Newborn 1 Yr-Old Tc-99m O.
30 minimum 3
4.78E -02 1.59E -01 1.95E + 01 9.02E + 00 (Pertechnetate) 12 5.10E-03 1.70E-02 2.08E + 00 9.63 E-01 24 2.58E-04 8.61E-04 1.05E-01 4.88E-02 48 6.638 - 07 2.21 E -06 2.70E-04 1.25 E -04 96 4.36E-12 1.45 E-11 1.77E-09 8.23 f'- 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 3.83 E + 02 a2 6.54E-01 2.18E + 00 2.66E + 02 1.23 E + 02 24 1.44E-01 4.81 E-01 5.88E + 01 2.73 E + 01 48 7.05E -03 2.35 E-02 2.87E + 00 1.33 E + 00 96 1.688 - 05 5.61 E-05 6.84E-03 3.17E -03 120 8.21E-07 2.74E-06 3.34E-04 1.55E-04 168 1.96E-09 6.53 E-09 7.97E-07 3.69E-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 Tc-99m PYP 20 minimum 3
1.73E-02 8.66E-02 4.81E + 00 2.05 E + 00 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-08 120 1.54E - 12 7.70E - 12 4.27E-10 1.82E-10 168 8.05 E-17 4.02E - 16 2.23 E-14 9.53 E-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 1.03 E + 01 12 3.49E-02 1.74E-01 9.68E + 00 4.13 E + 00 24 1.03 E-02 5.14E-02 2.85E + 00 1.22E + 00 48 8.90E-04 4.45E-03 2.47E-01 1.05E -01 96 6.68E-06 3.34E -05 1.85 E-03 7.91E-04 120 5.79E -07 2.90E-06 1.61 E-04 6.86E-05 168 4.35 E-09 2.17E-08 1.21 E-06 5.15 E -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 B.19 NUREG-1492
Table H.4 Total Activity logested and Internal Radiatien Doses Received from the intake of Radiopharmaceuticals in Hreast Milk Under Diff'erent Interruption Schedules (Continued)
Total Activity Effective Dose Equiva.'ent j
Administered laterruption Ing Med (nu em)
J Radio.
Activity Time pharmaceutical (mci)
Concentration (br)
(mci)
(%)
Newborn 1.Yr-Old
{
l Tc-99m RBC 20 minimum 3
3.53 E-03 1.76E -02 1.10E + 00 4.83 E-01 In Vitro Labeling 12 1.58E-03 7.92E-03 4.93E-01 2.17E-01 24 5.46E-04 2.73 E-03 1.70E-01 7.47E-02 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-04 120 1.08E-07 5.39E-07 3.35E-05 1.48E-05 168 1.52E-09 7.58E-09 4.71E-07 2.08E-07 336 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 maxmimum 3
6.06E-03 3.03E-02 1.88E + 00 8.30E -01 12 3.03E- 03 1.52E-02 9.42E-01 4.15E-01 24 1.20E-03 6.01E-03 3.74E-01 1.65E-01 48 1.90E-04 9.48E -04 5.89E-02 2.59E-02 96 4.70E-06 2.35E-05 1.46E-03 6.44E-04 120 7.41E-07 3.71 E-06 2.30E-04 1.01E-04 168 1.84E-08 9.20E-08 5.72E-06 2.52E-06 336 4.43 E-14 2.22E-13 1.38E-11 6.07E-12 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 Tc-99m RBC 20 minimum 3
9.49E-04 4.75E-03 2.88E-01 1.30E-01 i
in Vivo Labeling 12 3.79E-04 1.90E-03 1.15E-01 5.19E-02 24 1.12E-04 5.58E-04 3.39E-02 1.53 E-02 48 9.67E-06 4.84E-05 2.94E-03 1.32E -03 96 7.26E-08 3.63E-07 2.20E-05 9.94E-06 i
120 6.29E-09 3.15E-08 1.91E-06 8.62E-07 163 4.73 E-11 2.36E-10 1.43E -08 6.47E-09 336 4.57E-19 2.28E - 18 1.39E-16 6.25E-17 672 0.00E + 00 0.00E + 00 0.00E + 00 0.00E + 00 1
maxmimum 3
4.38E-01 2.19E + 00 1.33E + 02 5.99E + 01
)
12 1.80E-01 8.98E-01 5.45E + 01 2.46E + 01
)
24 5.48E-02 2.74E-01 1.668 + 01 7.50E + 00 1
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 4.45E-13 2.01 E-13 672 0.00E + 00 0.00E + 00 0.00B + 00 0.00E + 00 NUREG-1492 B.20 i
i Table B.4 Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued) l l
Administered Interruption Total Activity Effective Dose Equivalent Ingested (mrem)
Radio-Activity Time pharmaceutical (mci)
Concentration (hr)
(mci)
(%)
Newborn 1-Yr-Old Tc-99m 12 minimum 3
1.26E-02 1.05E-01 9.33E + 00 4.57E +00 Sulfur Colloid 12 3.74E-03 3.11E-02 2.76E + 00 1.35E + 00 24 7.38E-04 6.15E-03 5.46E-01 2.68E-01 48 2.8BE-05 2.40E-04 2.13E-02 1.05 E-02 96 4.40E-08 3.67E-07 3.26E-05 1.60E-05 120 1.72E-09 1.43E-08 1.27E-06 6.23E-07 168 2.62E-12 2.19E -11 1.94 E-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 6.3 BE +01 12 8.30E-02 6.92E-01 6.14E + 01 3.01E + 01 24 3.05E-02 2.54E-01 2.26E + 0!
1.11 E +01 48 4.11E-03 3.42E-02 3.04E + 00 1.49E + 00 96 7.47E-05 6.22E-04 5.53E-02 2.71E-02 120 1.01E-05 S.39E-05 7.45 E-03 3.65E-03 168 1.83 E-07 1.53E-06 1.35E -04 6.64E-05 336 1.48E-13 1.23 E-12 1.09E-10 5.36E-11 672 0.00E + 00 0.00E + 00 0.00E + 02 0.00E + 00 Tc-99m 30 minimum 3
4.78E-02 1.59E-01 1.95E + 01 9.02E + 00 White Blood Cdis*
12 5.10E -03 1.70E-02 2.08E + 00 9.63B-01 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
)
96 4.36E-12 1.45 E-11 1.77E-09 8.23 E-10 120 1.11 E-14 3.69E-14 4.508 -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
2.03 E + 00 6.76E + 00 8.25E + 02 3.83 E + 02 12 6.54E-01 2.18E + 00 2.66E + 02 1.23E + 02 24 1.44E-01 4.81E-01 5.88E +01 2.73 E + 01 48 7.05 E-03 2.35 E-02 2.87E + 00 1.33 E + 00 96 1.68E-05 5.61E-05 6.84E-03 3.17E-03 120 8.21E-07 2.74E-06 3.34E -04 1.55E-04 168 1.96E-09 6.53E-09 7.97E-07 3.69E-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
- The dose estimates for Tc-99m labeled white blood cells are actually the dose estimates for Tc-99m pertechnetate, as it was assumed that activity released in breast milk from this product would be in the form of pertechnetate.
B.21 NUREG-1492
i Table H.4 Total Activity Ingested and Internal Radiation Doses Received from the Intake of Radiopharmaceuticals in Breast Milk Under Different Interruption Schedules (Continued)
II Administered Interruption I"8 I'"'**I Radio-Activity Time pharmaceutical (mCl)
Concentration (hr)
(mci)
(%)
Newborn 1-Yr-Old T1-201 Chloride
- 3 minimum 3
1.22E-02 4.08E-01 1.94E + 02 1.11 E + 02 12 9.72E-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 7.73E + 01 4.42E + 01 96 2.45E-03 8.17E -02 3.84E + 01 2.19E + 01 120 1.76E-03 5.86E-02 2.76E + 01 1.578 + 01 168 9.10E-04 3.03 E-02 1.43E + 01 8.15 E + 00 336 9.11E-05 3.04E-03 1.43E + 00 8.15E-01 672 9.13 E -07 3.04E-05 1.43 E-02 8.17E-03
)
maxmimum 3
2.37E-02 7.91E-01 3.67E4 02 2.10E + 02 12 2.12E-02 7.08E-01 3.29E + 02 1.87E + 02 24 1.86E-02 6.21E-01 2.88E + 02 1.65E + 02 48 1.51 E-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 1.65 E + 02 9.43 E + 01 168 9.41E-03 3.14E-01 1.45E + 02 8.31E + 01 336 6.71 E-03 2.24E-01 1.04E + 02 5.93 E + 01 672 3.53E-03 1.18E-01 5.45E + 01 3.11E + 01 J
- Includes the done from radioactive contaminants. See Section B.1 CALCULATIONAL METHOD for details.
l NUREG-1492 B.22
[
Table H.5 Potential Doses to Breast-Feeding Infants from Radiopharmaceuticals Administered to a Woman if No Interruption of Hreast-Feeding and Recommendations on Interruption of Hreast-Feeding laternal Dose to External Dose to Maximum Infant if No Infant if No Administered laterruption of interruption of Recommendation 8
2 8
Radio-Activity Breast-Feeding Breast-Feeding Instructions on Interruption of pharmaceutical (mCl) (MBq)
(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 aboui 1 month I 123 mlBG' 10 (370) 300 100 yes Interruption for i
about 24 bours I123 0111' 2 0 4) 4-30 30 no None 1-123 Sodium 0.4 (14.8) 60-70 5
no None hxiide (Nal) 1 125 0111' O.01 (0.37) 0.2 10 no None 1131 O!H' O.3 (11.1) 3-20 70 no None I 131 Sodium 150 (5,550) very large NA' yes Complete cessation todide (Nal)
In-111 0.5 (18.5)40-200 60 yes Interruption for White Bhiod Cells about I week Tc-99m DISIDA 8 (300) 7-20 20 no None Tc-99m DTPA 20 040) 0.3-6 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 II 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 MAG 3' 10 (370) 0.2-3 30 no None Tc-99m MDP 20 040) 4-5 50 no None Tc-99m MIBI 30 (1,110) 1-10 80 no None Tc-99m 04 30 (1,110)20-800 80 yes Interruption for (Pertechnetate) about 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> Tc-99m PYP 20 040) 5-20 50 no None B.23 NUREG-1492 1
Table B.5 Potential Doses to Breast Feeding Infants from Radiopharmaceuticals Administered to a Woman if No laterruption of Breast-Feeding and Recommendations on Interruption of Breast-Feeding (Continued)
Internal Dose to External Dose to Maximum Infant if No Infant if No Administered Interruption of Interruption of Recommendation 1
s Radio-Activity Breest-Feeding
- Breast-Feeding lastructions on Interruption of pharmaceutical (mci) (MBq)
(mrem)
(mrem)
Required?'
Breast-Feeding 8
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 /> 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 Interruption for White Bkxx! Cells
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 Interruption for about 2 weeks
- 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. The 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 measurement varWJty 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. The external dose, typically small relative to the internal dose, is considered separately under Column 4.
- 3. Dose to the infant from external radiation only dunng 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.
- 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 done range for the newborn infant plus the external dose assuming no interruption of breast-feeding.
- 5. The duration of interruption is selected to reduce the maximum dose to a newborn infant to less than 0.1 rem. He actual doses that would be received by most infants would be far below 0.1 rem. De physician may use discretion in the recommendation, increasing or decreasing the duration of interruption.
- 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 administered 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 B.24
B.3 REFERENCES AH85 Ahlgren, L., S. Ivarsson, L.
IlE86 Hedrick, R.H., R.N. Di Simone, Johansson, S. Mattsson, B. Nosslin, R.L. Keen,1986, " Radiation 1985, " Excretion of Radionuclides in Dosimetry from Breast Milk Iluman Breast Milk After the Excretion of Radioiodine and Administration of Radiopharma.
Pertechnetale," J. Nucl. Med.
ceuticals," J. Nucl. Med. 26:1085.
27:1569.
BE73 Berke, R.A., E.C. Hoops, J.C.
HE79 Heaton, B.,1979, "The Build Up of Kerciakes, E.L. Saenger,1973, Technetium in Breast Milk j
" Radiation Dose to Breast-Feeding Following the Administration of Child After Mother has ""'Tc-MAA 7c"'O, Label'ed Macroaggregated Lung Scan," J. Nucl. Med.14:51.
Albumin," Br. J. Radiol. 52:149.
BU86 Butt, D. and K. Szaz,1986, 3095 Johnston, R.E., S.K. Mukherji, J.R.
" Indium-111 Radioactivity in Breast Perry, M.G. Stabin,1996, " Radiation Milk," Brit. J Radiol,59:80.
Dose from Breastfeeding Following Administration of TI-201," J. Nucl.
CR87 Cristy, M. and K. Eckerman,1987, Med. 37:2079.
" Specific Absorbed Fractions of Energy at Various Ages from KE94 Kettle, A.G., MJ. O'Doherty, P.J.
Internal Photons Sources, Blower,1994, " Secretion of ['"I]
ORNL/TM-8381 VI-V7, Oak Ridge I dide.m Breast Milk Following National Laboratory, Oak Ridge, TN.
Admmistration of [ Ij meta-i dobenzylguanidine," Eur. J. Nucl.
CR85 CranaEe, R. and M. Palmer,1985, Med. 21:181*
" Breast Milk Radioactivity After j
""'Tc-MAA Lung Studies," Eur. J.
Nucl. Med.11:257.
LA71 Larson, S.M. and G.L. Schall,1971
)
" Gallium-67 Concentration in DY88 Dydek, G.J. and P.W. Blue,1988, Human Breast Milk," (letter to the
" Human Breast Milk Excretion of editor) JAMA 218(2):257.
lodine-131 Following Diagnostic and Therapeutic Administration to a MA81 Mattsson, S., L. Johansson, B.
Lactating Patient with Graves' Nosslin, L. Ahlgren,1981," Excretion Disease," J. Nucl. Med. 29:407.
of Radionuclides in Human Breast Milk Following Administration of GR83 Greener, A.W., PJ. Conte, K.D.
'"I-fibrinogen,7c"'-MAA and Steidley,1983 " Update in Gallium-67 5'CR-EDTA," In Third International Concentration in Human Breast Radiopharmaceutical Dosimetry Milk," J. Nucl. Med. Technol.11:171.
Symposium; eds. E.E. Watson, A.T.
Schlafke-Stetson, J.L. Coffey, RJ.
HE88 Hesselwood, S.R., J.R. Thornback, Cloutier; HHS Publication FDA 81-J.M. BramelJ, 98F, " Indium-111 in 8166, U.S. Dept. of Health and Breast Milk Follovnng Administration Human Services, Food and Drug of Indium-111-Labeled Leukocytes,"
Administration, Rockville, MD, J. Nucl. Med. 29:1301.
pp 102-110.
B.25 NUREG-1492
M O89a Mountford PJ. and AJ. Coakley, OG83 Ogueleye, O.T.,1983, " Assessment 1989,A Review of the Secretion of of Radiation Dose to Infants from Radioactivity in Human Breast Milk:
Breast Milk Following the Data, Quantitative Analysis and Administration of ""'Tc Recommendations," Nucl. Med.
Pertechnetate to Nursing Mothers,"
Commun.10:15.
Health Physics 45:149.
Pl79 Pittard III, W.B., K. Bill, B.D.
)
M O89b Mountford, PJ. and AJ. Coakley, 1989, " Secretion of Radioactivity in Fletcher,1979, " Excretion of Breast Milk Following Administration Technetium m Human md, k," J.
Pediatrics 94:605.
of ml Hippuran," Br. J. Radiol.
62:388.
R O94 Robinson, P.S., P. Barker, A.
Campbell, P. Henson, I. Surveyor, M O87 Mountford, PJ. and AJ. Coakley, P.R. Young,1994, " lodine-131 in 1987 " Breast Milk Radioactivity Breast Milk Following Therapy for Following Injection of ""'Tc-Thyroid Carcinoma," J. Nucl. Med.
Pertechnetate and ""'Tc-35:1797.
Glucoheptonate," Nucl. Med.
Commun. 8:839.
RO90 Rose, M.R., M.C. Prescott, KJ.
Herman,1990," Excretion of M O85a Mountford, PJ. and AJ. Coakley, Iodine-123 Hippuran, 1985, " Excretion of Radioactivity in Technetium 99m Red Blood Cells, Breast Milk After an Indium leukocyte and Technetium-99m Scan," J. Nucl. Med. 26:1096.
Macroaggregrated Albumin into Breast Milk," J. Nucl. Med. 31:978.
M O85b Mountford, PJ., AJ, Coakley, F.M.
Hall,11985 " Excretion of RU94 Rubow, S., J. Klopper, H.
Radioactivity in Breast Milk Wasserman, B. Baard, M. van Following injection of Tc-99m Niekerk,1994 "The Excretion of DTPA," Nuc. Med. Commun. 6:341.
Radiopharmaceuticals in Breast Milk: Additional Data and D'
MOS4 Mountford, PJ., F.M. Hall, C.P.
Wells, AJ, Coakley,1984," Breast-RU91 Rubow, S., J. Klopper, P. Scholtz, Milk Radioactivity After a Tc-99m 1991,
- Excretion of Gallium-67 in DTPA Acrosol/Tc-99m MAA Lung Human Breast Milk and its Study," J. Nucl. Med. 25:1108.
Inadvertent Ingestion by a 9-Month-Old Child," Eur. J. Nucl. Med.18:829.
MU89 Murphy, P.H., C.W. Beasley, W.H.
. Moore, and M.G. Stabin,1989, RU88 Rubow, S. and J. Klopper,1988, j
" Thallium 201 in Human Milk:
" Excretion of Radioiodine in Human Observations and Radiological Milk Following a Therapeutic Dose Consequences," Health Physics of I-131," Eur. J. Nucl. Med.14:632.
56:539.
RU78 Rumble, W.F., R.L Aamodt, A.E.
NU52 Nurnberger, C.E. and A. Lipscomb, Jones, R. Henkin,1978, " Accidental 1952,' Transmission of Radioiodine Ingestion of Tc-99m in Breast Milk
(!*) to Infants Through Human by a 10-Week-Old Child," J. Nucl.
Maternal Milk," JAMA 150:1398.
Med.19:913.
l NUREG-1492 B.26
ST95 Stabin, M.,1995, " Internal Dosimetry WE94 Weiner, R.E. and R.P. Spencer, in Pediatric Nuclear Medicine," In "Quantification of Gallium-67 Citrate Pediatric Nuclear Medicine: ed.
in Breast Milk," Clin. Nucl. Med.
S. Treves; Springer Verlag, NY, 18:763.
TO76 Tobin, R.E. and P.B. Schneider, WE60 Weaver, J.C., M.L. Eamm, R.L.
1976 " Uptake of"Ga in the Lactating Dobson,1(Xi0 *Excr: tion of i
Breast and its Persistence in Milk:
Radioiodine in !!amn Milk," JAMA Case Report," J. Nucl. Med. 17:1055.
173:872.
VA71 Vagenakis, A.G., C.M. Abreau, L.E.
WY73 Wyburn, J.R., If.73, "Hutan Breast Braverman,1971 " Duration of Milk Excretion of RadionucLdes Radioactivity in the Milk of a Following Administretion of Nursing Mother Following *Tc Radiopharmaceuticals," J. Nucl.
Aministration," J. Nucl. Med.12:188.
Med.14:115.
B.27 NUREG-1492
m NRc FORM 336 u.0. NUCLEAR REGULATORY COMGMss40N
- 1. REPORT NUMBER G46 (Assigned by NRC, Add Vol. Supp., Rev.,
E3E' BIBLIOGRAPHIC DATA SHEET l
(See estuc6ans on the reverse)
- 2. TTTLE ANO sUeTrTLE Regulatory Analysis on Cnteria for the Release of Patients Administered Radioactive Material 3.
DATE REPORT PUBUSHED l
l Fin 11 Report MONN YEAR l
February 1997 j
- 5. AUTHOR (s)
- s. TYPE OF REPORT S. Schneider, SA McGuire Final
- 7. PERIOO COVERED (meAssee osass)
- 8. PERFORhaNG ORGANIZATION. NAME AND ADDRESS (FMtC, povade Duma omes or Regen. U S h Reo Aery conesam and mantag ask6ess. #centschr.
povane name end moohne edeess)
OMelon of Regulatory Applications Office of Nuclear Regulatory Research U.S. Nuclear Regulatory Commission Washington, DC 20555-0001
- 9. SPONSORING ORGANIZATION NAAE AND ADORESS (F NRC, fype "Same as e6ovet #contockr. pawnfo NRC Dvssen. Omco or Roonn (f $ Mme=a,andtry Cramum,
&&t ~..s)
S me as 8. above.
d
- 10. SUPPLESENTARY NOTES S. Schneider, NRC Project Manager
- 11. A8STRACT (200 eense or assa)
This regulatory analysis was developed to respond to three petitions for rulemaking to amend 10 CFR Parts 20 and 35 regarding release of patients administered radioactive material. The petitions requested revision of these regulations to remove the ambiguity that existed between the 1-mSv (0.1-rem) total effective dose equivalent (TEDE) public dose limit in Part 20 adopted in 1991, and tho activity-based release imit in 10 CFR 35.75 that, in some instances, would permit release of individuals in excess of the current public dose limit. Three altematives for resolution of the petitions were evaluated. Under Alternative 1, NRC would amend its patient release criteria in 10 CFR 35.75 to match the annual public dose Hmit in Part 20 of 1 mSv (0.1 rem) TEDE. Altemative 2 would maintain the status quo of using the activity-based release criteria currently found in 10 CFR 35.75. Under Altemative 3, the NRC would revise the release criteria in 10 CFR 35.75 to specify a dose imit of 5 mSv (0.5 rem) TEDE. The evaluation demonstrates that adoption of Alternative 1 would be considerably more expensive to the public compared to Alternative 2 (the status quo), primarily due to increased health care costs associated with more patients remaining in the hospital than under the current activity-based requirements. The evaluation also demonstrates that adoption of the 5-mSv (0.5-rem) dose limit under Alt:rnative 3 would result in a higher net value to the public compared to Alternatrve 2 (the status quo), primarily due to lower health cito costs and the increased psychological benefits to patients and their families by permitting earlier release from the hospital.
Based on this analysis, the decision was made that adoption of the 5-mSv (0.5-rem) TEDE Emit is consistent with the provisions in 10 CFR 20.1301(c), and the recommendations of the International Commission on Radiological Protection that an individual be i
a8 owed to receive annual doses up to 5 mSv (0.5 rem) TEDE under certain circumstances. Further, it no longer restricts patient release to a specific actMty, and therefore, permits release of patients with activities that are greater than currently aHowed. The primary benefit is in reduced hospital stays that provide emotional benefits to patients and their families, and result in lower health cif3 costs
- 12. KEY WORDSOESCRIPTORS (ust werva or piroses abat we assistiesearchers a meseng to report) 13 AvAsLAa:LrrY STATEMENT unlimited 10 CFR 35.75 14 SECURrrYCLAS$1FICATION patient release criteria iodine-131 crh,s e.ge) thirapeutic administration unclassified (Thos ReparQ unclassified
- 15. NUMBER OF PAGES
- 16. PRICE J
NRC FORM 335 Q4g) h form metah med W On FWwel Forms, he
i l
l 1
{
k Printed on recycled paper Federal Recycling Program
PATIENTS ADMINISTERED RADIOACTIVE MATERL\\L
. UNITED STATES SPECIAL STANDARD Mall NUCLEAR REGUI.ATORY COMMISSION POSTAGE AND FEES PAID WASHINGTON, DC 20555M1 USNRC PERMIT WJ. G47 120555139531 1 1A NIC J1'C0lR H1 US NRC-DADM OFFCIAL BUSINESS OIV FOIA PENALTY FOR PANATE USE, $300 TPS-PDR-NUREGE PUBLICATIONS.SVCS 2WFN-6E7 WASHINGTON DC 20555 L
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