ML20141J120
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8 I' % UNITED STATES
.S NUCLEAR REGULATORY COMMISSION E 'i WASHINGTON, D.C; 2006H001 g -
/ - -March 7.;1996J' -
MEMORANDUM TO: John E Glenn, Chief Radiation Protection and Health Effects Branch Division of Regulatory Applications, RES _
FROM: Donald A. Cool, Director- #
l Division of Industrial' and Medical Nuclear Safety.
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SUBJECT:
COMENTS ON THE REVISED FR ~ NOTICE ANO. REGULATORY >
' ANALYSIS FOR PATIENT RELEASE RULEMAKINGJ We have-reviewed the document package transmitting the Revised Regulatory Analysis for Patient Release Rulemaking, dated February 15, 1996, and the document package containing the revised Federal Reaister Notice for the rulemaking, dated February 22, 1996. We concur on both-documents, subject to the changes indicated by the pen-and-ink wording provided on the attached copies of the documents.
CONTACT: Larry W. Camper, 415-7231 Attachments: 1. Revised FRN for Patient Release Rulemaking
- 2. Revised Reg. Analysis for Patient Release Rulemaking i
gfl 00 9708150053 970807 PDR PR 20 62FR4120 PDR g'
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ROUTING AND TRANSMITTAL SLIP F bruary 15, 1996 TO: * * " * " " " " -
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- 1. L. Canner 'NMSS-fr
- 2. S. Treby '0GC
- 3. CC: J. Piccone - NMSS
- 4. B. Jones- OGC 5
X Actior_ File Note and Return Acoroval For Clearance Per Conversation As Reauested For Correction Preoare Reolv Circulate For Your Info See Me i Comment Investicate Sionature Coordination Justify REMARKS
SUBJECT:
REVISED REGULATORY ANALYSIS FOR PATIENT RELEASE RULEMAKING i) di o Attached for your review and comment is a revised draft ' N of the subject RA.
Please note:
g 1.
DUE DATES: ( ) 2/29/96 - Comments: to: RES2 3/5/95 --- Rulemaking pkg to EDO yok 2, A summary of major changes is attached.
3.
Q Revised FR notice will be forwarded to you for review and comments within several days. hn M
- 4. We will take care of- the format problems (e.g., an Th.QL V empty page) and the table of contents later.
SD M i
If you have any questions, please contact Stewart Schneider (415-6225) or Tony Tse (415-6233),
N CbM" g,p Thanks.
ph.y M FRON: (Name,org. symbol, Agency / Post) Room No.-Bldg. ?q D f d John Glenn - RES Phone No.
415-6187 ,
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2/15/96 S. Schneider PATIENT RELEASE CRITERIA MAJOR MODIFICATIONS TO REGULATORY ANALYSIS
- l. Costs per man-rem Original RA: Used $1,000 per person-rem.
Revised RA: Uses $2,000 per person-rem.
Rationale: The Commission adopted $2,000 per person-rem in late l 1995. The original RA was prepared with $1,000 per person-rem.
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- 2. Half-lives of radiopharmaceuticals in body Original RA: Used physical half-lives only.
Revised RA: Uses biological and effective half-lives.
Rationale: The physical half-lives were used to simply the computational model. With $1,000 per person-rem, this simplified model is sufficient to demonstrate the cost-effectiveness of the recommended alternative.
With $2,000 per person-rem, a more realistic model is necessary. Therefore, effective half-lives are used in the revised RA.
- 3. Use of uptake fractions for the thyroid and the rest of the body Original RA: Since only the physical half-lives were used, the use of uptake fractions was not necessary.
Revised RA: For thyroid ablation, uptake fractions for the thyroid (0.3, 0.4, 0.5, and 0.6) and the rest of the body (0.7, 0.6, 0.5, and 0.4) are used. (An average dose is estimated by averaging the four doses calculated by each set of uptake fractions.)
For thyroid cancer, an uptake fraction of 0.95 is used for the thyroid and an uptake fraction of 0.05 for the rest of the body, Rationale: When biological half-lives are used, the dose model requires the use of uptake fraction for various organs of the body.
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. 14; .Chanaes-to the conclusions based on the above modifications
~ As a result of the modifications discussed above .the following conclusions have been changed:;
A. Duration of hospital retention-of oatients and human research sub.iects (HRS) - Assumina Alt. 3 is adopted
- Original RA: About 10,000 days at a cost of approximately
$10M.
Revise RA: All can be released.- no_ hospital retention is necessary.
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-8. Cost benefit comparison between Alternative 3 (recommended) and Alternative 2 Original RA: Reduction in cost of hospitalization, loss.of time, and providing instructions: $8M Increase in detriment as a result of increasing s*
collective dose: $9M Net saving: About the same Revised-RA: Reduction in cost of hospitalization, -loss of time, and providing instructions: $14M Increase in detriment as a result of. increasing collective dose: $5M Net.saving: $9M
- 5. New Summary Table and Decision Rationale We added a summary table that shows the costs- and benefits (Table 4.14)-
and enhanced the discussion in the Decision Rationale section.
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NUREG 1492 Regulaton Analysis on Criteria for the Release of '
j Patients Administered Radioactive Material Final Report i -
. Prepared by:
Stewart Schneider and Stephen A. McGuire Omce of Nuclear Regulaton Research U.S. Nuclear Regulatory Commission Washington, D.C. 20555 -
February 15,1996 4
- NUREG.1492
_ .)
.> 4 4.2.3.2 Derapeutic Procedures The doses can be represented as a range where -
the range covers the minimum and the maximum The results of the dose calculations for transfer of radioactive material from published therapeutic procedures using the physical and -
data. The range is due to individual variability effective half lives (as applicable) are summarized and measurement variability as indicated by in Table 4.8. All calculations assume an concentrations measured in breast milk. The occupancy factor of 25 percent at a distance of doses were calculated for ne.vborn and one-year-1 meter and immediate release of the patient by old infants. Since the doses for newborn infants the licensee (i.e., no haspitalization). For are the highest, those doses were used in the hyperthyroidism (and thyroid ablation), doses analysis. The dose ranges for commonly used based on effective half life have been calculated radiopharmaceuticals assuming no interruption of using the four thyroidal uptake fractions that breast feeding are shown in column 3 of
' characterize the majority of patients with this Table B.4 (see Appendix B). The radionuclides in disease. Table 4.8 indicates that the model f - considering biological retention and climination provides dose estimates that are significantly less than the model that considers physical half-life only.
For the purposes of this analysis, the dose ,
estimates for lodine 131 based on the biological-model will be used because this model more closely reflects the behavior of iodine-131 in
g
- humans. For permanent unplants, biolog, cal i 3
f modeling does not apply, la this case, this - N analysis uses the dose estimates based on the physical half-life. Only the therapies involving k Lw radioiodine would be affected by any of the alternatives under consideration.
d k 4.2.4 Assessment of Doses to Breast-Feeding Infants
-If a radiopharmaceutical is administered to a -
woman who is breast-feeding, a fraction of the quantity administered will be deposited in the breast milh and will be transferred to the breast-feedeg infant. In considering the dose to -
- the individual likely to receive the highest dose from exposure n a patient who has been administered a radiopharmaceutical, it is necessary to consider both the internal and external dose to the infant from breast feeding.
4.2.4.1 Internal Dose The potentialinternal dose to the breast-feeding
- infant was calculated for the maximum normally administered quantities of commonly used diagnostic and therapeutic radiopharmaceuticals assuming no interruption in breast feeding. The results of the calculations are shown in Appendix B.
NUREG-1492 18
1' e i V Cq W,f y in reviewing Table B.4, it was concluded that the there could be two other people who will average recommendations on interruption of breast-feeding about half as much time near the patient. There to reduce the dose to the infant to less than 1 millisievert (0.1 rem) are practical and prudento p ' g/ average about a quarter as much time near the night also be about four other people who will that thei overwhelming majority of women would/ patient as the maximally exposed indhidual. The follo mstructions,and that there-ivmneason%r sum of the collective dose to all these people is siete tn nm% " hading 1 milHsiemt 3 times the dme to the maximally exposed indhidual,
@l-rem)-fiew LMW. The actual dosesj This situation could represent a typical family and that would be received by most infants for the friends. Of course some patients will rpend more recommended interruption periods shown should time near other people, but other patients wih be a small fraction of 1 millisievert (0.1 rem) due spend less. A collective dose of 3 times the dose to the conservatism of the analysis. For example, to the maximally exposed indhidual is thus a Q the internal dose to the breast. feeding infant from reasonable average representation.
p/ iodine-131 sodium iodide diagnatic and therapeutic procedures could exceed 5 millisleverts (0.5 rem) 44 . 4 f with no cessation of breast feeding. Ilowever,in F'mally, as data are not available on the distribution of the quantities of radionuclides
\ g these cases the licensee would instruct the woman administered for each therapeutic procedure, the
\ to cease breast-feeding. Consequently, for estimates of collective dose for each alternative i g iodine 131 sodium iodide, it is reasonable to are based on the typi:al activities used within the i i A assume that there would be no dose to nursing . ranges of activities administered and the l +
infants from breast-feeding. maximum activity used for thyroid ablation.
1' l \ 4.2.5 Collective Dose By using the results from Table 4.8, Tables 4.9, L 4.10, and 4.11 present the estimates of the
- k. ' To evaluate cach alternative, it is also necessary collective doses for Alternatives 1,2, and 3, to estimate not only the dose to the maximally respectively, for therapeutic administrations that h exposed individual, but also the collective dose to could be affected by the choice of alternative. For g other individuals who may be exposed to patients the typical administration of iodine-131 for thpoid dministered radioactive materials. To calculate ablation, this analysis uses 1.73 millisieverts precisely the collective dose that would be (0,173 rem) (the maximum likely dose to an received under any of the ahernatives would individual exposed to a patient assuming no require detailed information of a highly diverse hospitalization) as the basis for estimating the group of patients relative to lifestyles, thing collective doses. This value is the average of the arrangements, work environments, social activities, four doses calculated for the thpoidal uptake etc. This information does not exist and is fractions that characterize the majority of patients essentially impossible to precisely determine, in undergoing thyroid ablation. In a similar manner, place of a precise estimate we have made a rough the dose from the maximum quantity administered estimate of the collective dose per therapeutic (2,220 megabecquerels (60 millicuries)), was procedure which we believe is adequate for the determined to be 3.47 millisieverts (0347 rem).
purposes of this rulemaking. For thyroid cancer, this analysis uses
-1,86 millisleverts (0.186 rem) (assuming no 4.2.5.1 Collective Dose to Indhiduals hospitalization) as the basis for estimating the collective doses. Implants using iodine-125 are Based on considerations of the written instructions included because doses to exposed indhiduals provided patients, the demographics of the patient approach 1 millisievert (0.1 rem). However, population (see Table 4.3), and time, distance, Palladium 103 implants are not included because and shielding factors, we estimate that the doses to exposed individuals are always less than collective dose per procedure is 3 times the 1 millislevert (0.1 rem).
maximal dose (i.e., the dose to the most exposed indhidual). This 3 times factor could occur in the in Table 4.9 (Alternative 1), the collective dose following manner, based upon intuitive per procedure was determined in the following assumptions about a typical family and friends. In manner. It was assumed that all patients would addition to the person receiving the maximal dose, remain hospitalized until the dose dropped to who is likely to be the primary care-provider, I millisievert (0.1 rem). Thus, the dose to the NUREG-1492 22
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most exposed indhidual is 1 millislevert (0.1 rem).
For indine 125 implants, the dose is already less .
than 1 millisievert (0.1 rem) so no hospitalization I I
is required. The collective dose per procedure is then assumed to be 3 times the dose to the most exposed indhidual.
Under Alternative 1, patients administered the typical and maximum quantities of lodine 131 for thyroid ablation require aboct 7 and 14 days of
~
hospitalization, respectively, before release can be authorized. Wherease, thyroid cancer patients administered the typical quantity of iodine 131 require about 1.5 days of hospitalization, i
in Table 4.10 (Alternative 2), the collective dose per procedure was evaluated in the following i manner. For thyroid ablations using the typical C
)( aethity of iodice-131, no hospitalization is . mred since the acthity is equal to the release limit of ,
1,110 megabecquerels (30 millicuries). The collective dose is 3 times the irdividual dose (i.e.,
1,73 millisleverts (0.171 rem)) or 5.2 millisleverts (0.52 rem). On the other hand, patients administered the maxium activity require about 1 day of hospitalization before release can be authorized. When released, the maximum dose from these patients will be greater than the dose from a patient administered 1,110 megabecquerels (30 millicuries) due to biologics'
- Idcrations.
The estimated dose to the ms c ' indivual o dose is is 3 millisieverts (0.3 rem). T* .
3 times the indhidual dose or , <
(0.9 rem). The collective dose t 23 NUREG-1492
Table 4.9 Estimates of Collective Dose from herapeutic Radiolodine Procedures for Alternative it Annual Limit of 1 millislevert (0.1 rem)
Typical Activity Collecti e Estimated Total Therapeutic Administered Dose / Procedure Procedures Collective Dose Procedure (Milq) (mCl) (mSv) (rem) per Year (person Sv (rem))
Thyroid Ablation 3 !
- iodine 131 1,110 (30) 3.0 (03) 49,000 147 (14,700) l 2,220"8 (60) 3.0 (03) 1 mi 9 (300)
[. b Thyroid Cancer VM
- iodine-131 5,550 (150) 3.0 (03) 10,000 30 (3,000) /
Permanent Implant iodine 125 1,480 (40) 2.2 (0.22) 2,000 4.4 (440)
All Therapeutic Procedures 62,000 184.4 (18,440)
"5 Maximum activity administered, his analysis assumes that 98 percent of the patients are typically administered 1,110 millisieverts 00 millicuries) and that 2 percent'are administered the maximum quantity.
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t 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 Typical Activity Collective Estimated Total Herapeutic Administered Dose / Procedure Procedures Collective Dose Procedure (Milq) (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) 9.0 (0.9) 1,000 9 (900)
Thyroid Cancer
- iodine 131 5,550 (150) 3.0 (03) 10,000 30 (3,000)
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. His analysis assumes that 98 percent of the patients are typically administered 1,110 millisieverts 00 millicuries) and that 2 percent are administered the naximum quantity.
NUREG 1492 24
technetium-99m pertechnetate administrations), it is estimated that approximately . _
= As discussed above,13.5 percent of the 17,200 procedures per year would be subject to radiopharmaceuticals are administered to females these requirements (i.e., (1) 10,000 patients of childbearing age and that 5 percent of them treated with iodine for thyroid cancer and could be breast feeding. To estimate the number (2) 7,200 administrations to breast feeding of releases that require a record, one needs only women). A cost of $17 per patient is estimated.
multiply 1.06 million by 13.5 percent, and then by 5 percent. Thus,7,200 releases of breast. feeding This results in an annual estimated cost of approximately $03 million.
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women re quire a record. 9 43.1.2 Derivation of Indirect Costs Costs of Providing Instructions Y 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 o imposes additional costs for providing instructions, retained in a controlled environment. = Indirect 4 including written instructions, on the estimated costs may also be incurred by individuals other 1,350 licensees. In the case in which the than the patient who may forego economic administered activity could cause a dose from activities to accommodate a family member's direct radiation exceeding 0.1 rem (1 millislevert), hospital retention. Economic activities include *
}'
instructions would have to be given to 62,000 occupational work that is lost to either the patiert patients per year at a cost of $1.4 million per year. or his or her employer as well as non-occupation in addition, instructions would have to be given to al (e.g., domestic) work which must be performe
( approximately 27,000 breast-feeding women at a by someone else at the expense of the patient.
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cost of $0.6 million per par. In both cases, a cost ff $22 per patic2)s estimated. The total The conversion of time lost from economic estimated cost of instructions is $2 million per year. activities to equivalcat dollars is most fairly M ' 7' ' achieved by means of the gross national product Costs of Providing Recordkeeping (GNP). The GNP is considered the most comprehensive measure of the country's economic Alternatives 1 and 2 have no recordkeeping activity and includes the market value of atl goods requi ements, and therefore, have no related and services that have been bought for final use costs. . However, the rule associated with ~ during a year. From the GNP of about
. Alternative 3 imposes additional paperwork and $5,600 billion in 1991, the gross average annual recordkeeping requirements on the estimated per capita income of about $22,000 is derived.
1,350 licensees (NRC- and Agreement State. The value of $22,000 per year corresponds to licensed) that provide diagnostic and therapeutic $60 per day. To estimate the equivalent dollar administrations of radiopharmaceuticals. For value for the number of days lost due to retention therapeutic administrations where releases are not of an individual for a therapeutic procedure, one based on the default table of activities and dose needs only multiply $60 by the days of retention rates in Regulatory Guide 839," Release of for the procedure presented in Table 4.12. The Patients Administered Radioactive Materials" value of the days lost for each alternative is shown (NRC96), a record must be maintained for 3 years, in Table 4.13.
A_dditionally, if the released patient is a breast- 43.13 Evaluation of Psychological Costs feeding woman and the radiation dose to the nur.ing infant could result in a total effective dose Retention of patients in a hospital by design equivalent exceeding 5 millisievert (0.5 rem) necessitates that the patient be " isolated
- and that assuming no interruption of breast feeding, then a human contact, inclusive of family m:mbers, is record must be maintained, for 3 years, that instructions were provided. In this case, both diagnostic and therapeutic administrations of radiopharmaceuticals could require a record.
NUREG-1492 28
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Table 4.13 Annual Attributes of Alternati es 1,2, and 3 S# p
}
[ Costhstimates llospitalization Value of Records & \
llospital cost lost tim -
Instructions 'sychologies I Collective Dose Retention 5 $ $ cost Alternative (person rem) (days) (millions) (millions (millions) (relative) 1 18,400 427,000 427 25.62 0 liigh !d 2 29,840 16,000 16 0.96 0 Moderate 3 32,580 0 0 O 2.3 Low
- {
d either avoided or minimized. Such isolation may that an evaluation, as explained above, is highly bring about numerous changes and impositions in subjective and dependent upon the indhidual the lives of the patient and family members that situation. Instead, this analysis uses a qualitative may in part be linked to, but are not reflected in, and reasonable approach to scope the range of the direct and indirect economic costs identified possible responses. As shown in Table 4.13, above. The wide variety of deterioration in the comparison is provided on a relative scale, quality of life brought on by illness are frequently referred to as psychological costs. For thyroid 4.3.2 Costs and Benefits of Alternatives cancer or dysfunction requiring therapeutic doses of iodine 131 for example, a deterioration in the Table 4.13 summarizes the data pertaining to the
( quality of life may be precipitated by the loss of annual attributes for each of the three alternatives
} bodily function, a lifetime dependence on under consideration. To determine the preferred j medication, hormonal instability, uncertainty of alternative, the costs and benefits that result when normal life-expectancy, disruption of normal daily Alternatives 1 and 3 are each compared with routines, and reduced financial security related to Alternative 2 (the status quo) were analyzed. The
! cmployment, lost earnings, and medical expenses, results are shown in Table 4.14. A value of $2,000 I
per person rem was used as the ccnversion factor 3b While some of these elements of psychological for dose averted. I costs are the result of the disease itself, others such as disruption of normal routines, social Uccause the benefits and costs for all alternatives j isolation, and enhanced financial strain are clearly occur in the same year, and remain the same cach 4*
l clements of psychological costs that are directly related to pat retention [ha terizi year for the therapeutic procedures discussed, a dicounted flow of the benefits and costs of this l
l psychblogical cost Thomas H on (HO84) rulemaking is not required.
l ehief economist for t Depa ent of Health and
, Iluman Services' Office o nalysis and Epidemiology states: * . The environment
, 4.4 Evaluation of the Alternatives created by illness oft mduecs anxiety, reducep self esteem and fe ngs of we being, resentmgnt, With Respect to Accepted and emotional p blems that oft require Radiation Protection Principles
/.,
psychotherapy Problems of thing arrangements' g
may develo behav or p leading to family conflicthntisocialk Selection of the 5-millisieverts (0.5-rem) total y
' finan stram% . . . Theproblems
-and psychological combination can be ofeffective dose equivalent per year criterion is consistent with: the Commission's provision in lly devastating
' - " , 10 CFR 20.1301(c) for authorizing a licensee to operate up to this limit; the recommendations of The conversion of psychological cost from patient the International Commission on Radiological retention to equivalent dollars is complex such 31 N1JREG-1492
Table 4.14 Annual Costs and lienefits of Alternatives 1 and 3 Codipared to Alternative 2 (The Status Quo)
) f Collective-Dose # Costs Assocated llospitalization, Lost Time, Value Records and lustructions Net lienefit Dose Aterted 5 $ $
Alternathe (person-rem) (millions) (millions) (millions)
-1 11,440 22 (savings) 435 (cost) -412 (net cost) 2 0 0 0 0 3 -2,740 5 (cost) 14 (savings) 9 (net savings)
A footnote will explain the how the numbers were rounded off, 33 NUREG-1492
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n Table HA Potential Doses to Breast Feeding Infants from Radiopharmaceuticals Administered to a Woman if No laterruption of Hreast Feeding and Recommendatloas on Interruption of Breast Feeding Internal Dose to External Dose to Maximum Infant if No Infant if No Administered interruption of Interruption of Recommendation Radio- Activity' Breast-Feeding8 Breast-Feeding 3 Instructions on Interruption of pharmaceutical (mci) (MBq) (mrem) (mrem) Required?' Breast-Feedings 1131 Nel 150 (5,550) very large NA' yes ' C'omplete cessation is necessary to avoid thyroid ablation in the '
infang ,
1-123 Nat 0.4 (14.8) 60 5 no q 1-123 O!H 2 64) 4-30 30 ) MO None I-123 m!BG 10 070) 300 100 yes Interruption for kh about 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> 1125 OIH 0.01 (0.37) 0.2 10 no None l l-131 0111 0.3 (11,1) 3-20 70 no None Tc-99m DTPA 20 040) 0.3-6 50 no None Tc-99m MAA 4 (148) 4-300 10 yu Interrupdon for about 12 hours1.388889e-4 days <br />0.00333 hours <br />1.984127e-5 weeks <br />4.566e-6 months <br /> Tc-99m 04 30 (1,110)20-800 80 ys 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 DISIDA 8 000) 4-20 20 no None Tc-99m 20 040) 2-5 50 no None Glucoheptonate Tc-99m flAM 8 000) 20-50 20 no None Tc-99m MIDI 30 (1,110) 1-10 80 no None Tc-99m MDP 20 040) 4-5 50 no None Tc-99m PYP 20 040) 5-20 50 no None 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 RBC 20 040) 1-2 50 no None in vitro labeling 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 /> Tc-99m DTPA 1 (37) 0.02 0.3 3 no None Aerosol ,
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I B.21 NUREG-1492
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