ML19157A111

Preliminary Draft Proposed Regulatory Guide 8.39, Release of Patients Administered Radioactive Materials, Revision 1 (Phase 1) for ACMUI Review with Note

ML19157A111
Person / Time
Issue date:	06/06/2019
From:	Office of Nuclear Material Safety and Safeguards
To:
Jamerson, Kellee
References
RG-8.039
Download: ML19157A111 (32)

Text

IMPORTANT NOTE Regulatory Guide (RG) 8.39, Release of Patients Administered Radioactive Material, is being revised in two phases.

Phase 1 updates the patient release guidance, including information for patient instructions and updates to Table 3, Activities of Radiopharmaceuticals that Require Instructions and Records When Administered to Patients who are BreastFeeding an Infant or Child, as well as a new section, Death of a Patient Following Radiopharmaceutical Administration or Implants.

Phase 2 updates the dosimetric equations, methodologies, and tables used to calculate dose to members of the public from released patients.

The enclosed document is the Preliminary Draft Proposed RG 8.39, Revision 1 and only pertains to the Phase 1 updates. This preliminary draft was provided to the ACMUI for its review and comment for NRC staffs consideration. After the NRC staff evaluates the ACMUIs comments, the Draft RG 8.39 will be published in the Federal Register for public comment.

U.S. NUCLEAR REGULATORY COMMISSION REGULATORY GUIDE 8.39, REVISION 1 Issue Date: March 2019 Technical Lead: Said Daibes Figueroa PRELIMINARY DRAFT FOR ACMUI REVIEW RELEASE OF PATIENTS ADMINISTERED RADIOACTIVE MATERIALS INTRODUCTION Purpose This regulatory guide (RG) provides guidance to the licensee on determining (1) when the licensee may authorize the release of a patient who has been administered radiopharmaceuticals or implants containing radioactive material, (2) when instructions to the patient are required, and (3) when records are required to be generated and maintained. The RG lists activities for commonly used radionuclides and their corresponding dose rates with which a patient may be released in compliance with the applicable dose limits.

Applicability This RG applies to all US Nuclear Regulatory Commission (NRC) licensees subject to Title 10 of the Code of Federal Regulations (10 CFR), Part 35.75, Release of individuals containing unsealed byproduct material or implants containing byproduct material (Ref. 1).

Applicable Regulations

• 10 CFR 35.75 permits licensees to authorize the release from its control of any individual who has been administered radiopharmaceuticals or implants containing radioactive material if the total effective dose equivalent to any other individual from exposure to the released individual is not likely to exceed 5 millisieverts (0.5 rem). In this guide, the individual to whom the radioactive material has been administered is called the patient.

• 10 CFR 35.75(b) requires that the licensee provide the released individual with instructions, including written instructions, on actions recommended to maintain doses to other individuals as low as is reasonably achievable if the total effective dose equivalent to any other individual is This RG is being issued in draft form to involve the public in the development of regulatory guidance in this area. It has not received final staff review or approval and does not represent an NRC final staff position. Public comments are being solicited on this draft regulatory guide (DG) and its associated regulatory analysis. Comments should be accompanied by appropriate supporting data.

Comments may be submitted through the Federal rulemaking Web site, http://www.regulations.gov, by searching for draft regulatory guide DG-XXXX. Alternatively, comments may be submitted to the Rules, Announcements, and Directives Branch, Office of Administration, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001. Comments must be submitted by the date indicated in the Federal Register notice.

Electronic copies of this DG, previous versions of DGs, and other recently issued guides are available through the NRCs public Web site under the Regulatory Guides document collection of the NRC Library at https://nrcweb.nrc.gov/reading-rm/doc-collections/reg-guides/. The DG is also available through the NRCs Agencywide Documents Access and Management System (ADAMS) at http://www.nrc.gov/reading-rm/adams.html, under Accession No. MLXXXXXXXXX. The regulatory analysis may be found in ADAMS under Accession No. MLXXXXXXXXX.

likely to exceed 1 millisievert (0.1 rem). If the dose to a breast-feeding infant or child could exceed 1 millisievert (0.1 rem) assuming there were no interruption of breast-feeding, the instructions shall also include (1) guidance on the interruption or discontinuation of breast-feeding and (2) information on the consequences of failure to follow the guidance.

• 10 CFR 35.75(c) requires that the licensee maintain a record of the basis for authorizing the release of an individual, for 3 years after the date of release, if the total effective dose equivalent is calculated by (1) using the retained activity rather than the activity administered, (2) using an occupancy factor less than 0.25 at 1 meter, (3) using the biological or effective half-life, or (4) considering the shielding by tissue.

• 10 CFR 35.75(d), the licensee is required to maintain a record, for 3 years after the date of release, that instructions were provided to a breast-feeding woman if the radiation dose to the infant or child from continued breast-feeding could result in a total effective dose equivalent exceeding 5 milliSieverts (0.5 rem).

Related Guidance

• NUREG-1556, Volume 9, Consolidated Guidance About Materials Licenses: Program-Specific Guidance About Medical Use Licenses, (Ref. 2)

• NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material, (Ref 3)

Purpose of Regulatory Guides The NRC issues RGs to describe to the public methods that the staff considers acceptable for use in implementing specific parts of the agencys regulations, to explain techniques that the staff uses in evaluating specific problems or postulated events, and to provide guidance to applicants. RGs are not substitutes for regulations and compliance with RGs is not required. Methods and solutions that differ from those set forth in RGs will be deemed acceptable if they provide a basis for the findings required for the issuance or continuance of a permit or license by the Commission.

Paperwork Reduction Act This RG provides guidance for implementing the information collections in 10 CFR Parts 35 that are subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et. seq.). These information collections were approved by the Office of Management and Budget (OMB), under control numbers 3150-0011 and 3150-0151. Send comments regarding this information collection to the Information Services Branch, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, or by e-mail to Infocollects.Resource@nrc.gov, and to the Desk Officer, Office of Information and Regulatory Affairs, NEOB-10202 (3150-0011, 3150-0151), Office of Management and Budget, Washington, DC 20503.

RG 8.39, Rev. 1, Page 2

Public Protection Notification The NRC may not conduct or sponsor, and a person is not required to respond to, a collection of information unless the document requesting or requiring the collection displays a currently valid OMB control number.

RG 8.39, Rev. 1, Page 2

TABLE OF CONTENTS A. INTRODUCTION .................................................................................................................................. 1 B. DISCUSSION ......................................................................................................................................... 4 C. STAFF REGULATORY GUIDANCE .................................................................................................. 7

1. Release Criteria ............................................................................................................................. 7 1.1 Release of Patients Based on Administered Activity .................................................................. 7 1.2 Release of Patients Based on Measured Dose Rate ...................................................................... 7 1.3 Release of Patients Based on Patient-Specific Dose Calculations ................................................ 9

2. Instructions ..................................................................................................................................... 9 2.1 Activities and Dose Rates Requiring Instructions ....................................................................... 9 2.2 Additional Instructions for Release of Patients Who Could be Breast-Feeding after Release .. 11 2.3 Content of Instructions ............................................................................................................... 13 2.3.1 Pre-Treatment Discussions Regarding Radiopharmaceutical Administrations ....................... 14 2.3.2 Patient Precautions................................................................................................................... 15 2.3.3 Patient Instructions .................................................................................................................. 16 2.3.4 Patient Acknowledgement of Instructions17 2.4 Death of a Patient Following Radiopharmaceutical or Implants Administrations ..................... 17 2.5 Precautions for Long-lived Contaminants in Radiopharmaceutical Therapy ............................. 18

3. Records ........................................................................................................................................ 18 3.1 Records of Release...................................................................................................................... 18 3.2 Records of Instructions for Breast-Feeding Patients .................................................................. 19

4. Summary Table ............................................................................................................................ 20 D. IMPLEMENTATION........................................................................................................................... 21 REFERENCES ..................................................................................................................................... 22 APPENDIX A .....................................................................................................................................A-1 APPENDIX B ..................................................................................................................................... B-1 RG 8.39, Rev. 1, Page 3

B. DISCUSSION Reason for Revision This revision of RG 8.39 provides updated NRC patient release guidance that includes information for patient instructions and updates to Table 3 (Activities of Radiopharmaceuticals that Require Instructions and Records When Administered to Patients who are Breast-Feeding an Infant or Child). By updating the NRC guidance with this information, the patient will be better informed and can make better choices in following the instructions. This revision does not update the technical information, i.e., equations, methods, and tables, contained herein.

Background

The activities at which patients could be released were calculated by using, as a starting point, the method discussed in the National Council on Radiation Protection and Measurements (NCRP) Report No. 37, Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides, (Ref 4).

NCRP Report No. 37 uses the following equation to calculate the exposure until time t at a distance r from the patient:

0.693 34.6 (1 )

() = (Equation 1) r2 Where D(t) = Accumulated exposure at time t, in roentgens, 34.6 = Conversion factor of 24 hrs/day times the total integration of decay (1.44),

= Specific gamma ray constant for a point source, R/mCi-hr at 1 cm, Q0 = Initial activity of the point source in millicuries, at the time of the release, Tp = Physical half-life in days r = Distance from the point source to the point of interest in centimeters, t = Exposure time in days.

This guide uses the NCRP equation (Equation 1) in the following manner to calculate the activities at which- patients may be released.

• The dose to an individual likely to receive the highest dose from exposure to the patient is taken 0.693 to be the dose to total decay. Therefore, 1 is set equal to 1.

• It is assumed that 1 roentgen is equal to 10 millisieverts (1 rem).

• The exposure rate constants and physical half-lives for radionuclides typically used in nuclear medicine and brachytherapy procedures are given in Appendix A to this guide.

• Default activities at which patients may be released are calculated using the physical half-lives of the radionuclides and do not account for the biological half-lives of the radionuclides.

RG 8.39, Rev. 1, Page 4

• When release is based on biological elimination (i.e., the effective half-life) rather than just the physical half-life of the radionuclide, Equation 1 is modified to account for the uptake and retention of the radionuclide by the patient as discussed in Appendix B.

• For radionuclides with a physical half-life greater than 1 day and no consideration of biological elimination, it is assumed that the individual likely to receive the highest dose from exposure to the patient would receive a dose of 25 percent of the dose to total decay (0.25 in Equation 2) at a distance of 1 meter. Selection of 25 percent of the dose to total decay at 1 meter for estimating the dose is based on measurements discussed in the supporting regulatory analysis (Ref. 3) that indicate the dose calculated using an occupancy factor, E, of 25 percent at 1 meter is conservative in most normal situations.

• For radionuclides with a physical half-life less than or equal to 1 day, it is difficult to justify an occupancy factor of 0.25 because relatively long-term averaging of behavior cannot be assumed.

Under this situation, occupancy factors from 0.75 to 1.0 may be more appropriate.

Thus, for radionuclides with a physical half-life greater than 1 day:

34.6 (0.25)

() = (Equation 2)

(100 cm)2 For radionuclides with a physical half-life less than or equal to 1 day and if an occupancy factor of 1.0 is used:

34.6 (1)

() = (100 cm)2 (Equation 3)

Equations 2 and 3 calculate the dose from external exposure to gamma radiation. These equations do not include the dose from internal intake by household members and members of the public because the dose from intake by other individuals is expected to be small for most radiopharmaceuticals (less than a few percent) relative to the external gamma dose (see Section B.3, Internal Dose, of Appendix B). Further, the equations above do not apply to the dose to breast-feeding infants or children who continue to breast-feed. Patients who are breast-feeding an infant or child must be considered separately, as discussed in Staff Regulatory Guidance 1.1, Release of Patients Based on Administered Activity.

Documents Discussed in Staff Regulatory Guidance This RG endorses the use of one or more codes or standards developed by external organizations, and other third party guidance documents. These codes, standards and third party guidance documents may contain references to other codes, standards or third party guidance documents (secondary references).

If a secondary reference has itself been incorporated by reference into NRC regulations as a requirement, then licensees and applicants must comply with that standard as set forth in the regulation. If the secondary reference has been endorsed in a RG as an acceptable approach for meeting an NRC requirement, then the standard constitutes a method acceptable to the NRC staff for meeting that regulatory requirement as described in the specific RG. If the secondary reference has neither been incorporated by reference into NRC regulations nor endorsed in a RG, then the secondary reference is RG 8.39, Rev. 1, Page 5

neither a legally-binding requirement nor a generic NRC approved acceptable approach for meeting an NRC requirement. However, licensees and applicants may consider and use the information in the secondary reference, if appropriately justified, consistent with current regulatory practice, and consistent with applicable NRC requirements.

RG 8.39, Rev. 1, Page 6

C. STAFF REGULATORY GUIDANCE This section provides detailed descriptions of the methods, approaches, or data that the NRC staff considers acceptable for meeting the requirements of the applicable regulations cited in the Introduction.

1. Release Criteria Licensees should use one of the following options to release a patient who has been administered radiopharmaceuticals or implants containing radioactive material in accordance with regulatory requirements.

1.1 Release of Patients Based on Administered Activity In compliance with the dose limit in 10 CFR 35.75(a), licensees may release patients from licensee control if the activity administered is no greater than the activity in Column 1 of Table 1. The activities in Table 1 are based on a total effective dose equivalent of 5 millisieverts (0.5 rem) to an individual using conservative assumptions of (1) administered activity, (2) physical half-life, (3) occupancy factor of 0.25 at 1 meter for physical half-lives greater than 1 day, and, for conservatism, an occupancy factor of 1 at 1 meter for physical half-lives less than or equal to 1 day, and (4) no shielding by tissue. The total effective dose equivalent is approximately equal to external dose because the internal dose is a small fraction of the external dose (see Section B.3, Internal Dose, of Appendix B). In this case, no record of the release of the patient is required unless the patient is breast-feeding an infant or child as discussed in Regulatory Position 3.2, Records of Instructions for Breast-Feeding Patients. The licensee may demonstrate compliance by using the records of activity that are already required by 10 CFR 35.32 and 35.53.

If the activity administered exceeds the activity in Column 1 of Table 1, the licensee may release the patient when the activity has decayed to the activity in Column 1 of Table 1. In this case, a record is required by 10 CFR 35.75(c) because the patients release is based on the retained activity rather than the administered activity. The activities in Column 1 of Table 1 were calculated using either Equation 2 or 3, depending on the physical half-life of the radionuclide.

If a radionuclide not listed in Table 1 is administered, the licensee can demonstrate compliance with the regulation by maintaining, for NRC inspection, a calculation of the release activity that corresponds to the dose limit of 5 millisieverts (0.5 rem). Equation 2 or 3 may be used, as appropriate, to calculate the activity Q corresponding to 5 millisieverts (0.5 rem).

The release activities in Column 1 of Table 1 do not include consideration of the dose to a breast-feeding infant or child from ingestion of radiopharmaceuticals contained in a patients breast milk.

When the patient is breast-feeding an infant or child, the activities in Column 1 of Table 1 are not applicable to the infant or child. In this case, it may be necessary to give instructions as described in Staff Regulatory Guidance 2.2 and 2.3 as a condition for release. If failure to interrupt or discontinue could result in a dose to the breast-feeding infant or child in excess of 5 millisieverts (0.5 rem), a record that instructions were provided is required by 10 CFR 35.75(d).

1.2 Release of Patients Based on Measured Dose Rate Licensees may release patients to whom radionuclides have been administered in amounts greater than the activities listed in Column 1 of Table 1 provided the measured dose rate at 1 meter (from the surface of the patient) is no greater than the value in Column 2 of Table 1 for that radionuclide. In this case, RG 8.39, Rev. 1, Page 7

however, 10 CFR 35.75(c) requires a record because the release is based on considering shielding by tissue.

Table 1. Activities and Dose Rates for Authorizing Patient Releasea COLUMN 1 COLUMN 2 ACTIVITY AT OR BELOW DOSE RATE AT 1 METER, AT OR WHICH PATIENTS MAY BE BELOW WHICH PATIENTS MAY RELEASED BE RELEASEDb RADIONUCLIDE (GBq) (mCi) (mSv/hr) (mrem/hr)

Ag-111 19 520 0.08 8 Au-198 3.5 93 0.21 21 Cr-51 4.8 130 0.02 2 Cu-64 8.4 230 0.27 27 Cu-67 14 390 0.22 22 Ga-67 8.7 240 0.18 18 I-123 6.0 160 0.26 26 I-125 0.25 7 0.01 1 I-125 implant 0.33 9 0.01 1 I-131 1.2 33 0.07 7 In-111 2.4 64 0.2 20 Ir-192 implant 0.074 2 0.008 0.8 P-32 (c) (c) (c) (c)

Pd-103 implant 1.5 40 0.03 3 Re-186 28 770 0.15 15 Re-188 29 790 0.20 20 Sc-47 11 310 0.17 17 Se-75 0.089 2 0.005 0.5 Sm-153 26 700 0.3 30 Sn-117m 1.1 29 0.04 4 Sr-89 (c) (c) (c) (c)

Tc-99m 28 760 0.58 58 Tl-201 16 430 0.19 19 Y-90 (c) (c) (c) (c)

Yb-169 0.37 10 0.02 2

a. The activity values were computed based on 5 millisieverts (0.5 rem) total effective dose equivalent.

b. If the release is based on the dose rate at 1 meter in Column 2, the licensee must maintain a record as required by 10 CFR 35.75(c) because the measurement includes shielding by tissue. See Staff Regulatory Guidance 3.1, Records of Release, for information on records.

c. Activity and dose rate limits are not applicable in this case because of the minimal exposures to members of the public resulting from activities normally administered for diagnostic or therapeutic purposes.

NOTES: The millicurie values were calculated using Equations 2 or 3 and the physical half-life. The gigabecquerel values were calculated based on the millicurie values and the conversion factor from millicuries to gigabecquerels. The dose rate values are calculated based on the millicurie values and the exposure rate constants. In general, the values are rounded to two significant figures. However, values less than 0.37 gigabecquerel (10 millicuries) or 0.1 millisievert (10 millirems) per hour are rounded to one significant figure.

Details of the calculations are provided in NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material (Ref. 3). Agreement State regulations may vary. Agreement State licensees should check with their State regulations prior to using these values.

RG 8.39, Rev. 1, Page 8

If a radionuclide not listed in Table 1 is administered and the licensee chooses to release a patient based on the measured dose rate, the licensee should first calculate a dose rate that corresponds to the 5 millisievert (0.5 rem) dose limit. If the measured dose rate at 1 meter is no greater than the calculated dose rate, the patient may be released. A record of the release is required by 10 CFR 35.75(c). The dose rate at 1 meter may be calculated from Equation 2 or 3, as appropriate, because the dose rate at 1 meter is equal to Q/10,000 cm2.

1.3 Release of Patients Based on Patient-Specific Dose Calculations Licensees may release patients based on dose calculations using patient-specific parameters.

With this method, based on 10 CFR 35.75(a), the licensee must calculate the maximum likely dose to an individual exposed to the patient on a case-by-case basis. If the calculated maximum likely dose to an individual is no greater than 5 millisieverts (0.5 rem), the patient may be released. Using this method, licensees may be able to release patients with activities greater than those listed in Column 1 of Table 1 by taking into account the effective half-life of the radioactive material and other factors that may be relevant to the particular case. If the dose calculation considered retained activity, an occupancy factor less than 0.25 at 1 meter, effective half-life, or shielding by tissue, a record of the basis for the release is required by 10 CFR 35.75(c).

Appendix B contains procedures for performing patient-specific dose calculations, and it describes how various factors may be considered in the calculations.

2. Instructions 2.1 Activities and Dose Rates Requiring Instructions Based on 10 CFR 35.75(b), for some administrations the released patients must be given instructions, including written instructions, on how to maintain doses to other individuals as low as is reasonably achievable (ALARA) after the patients are released. Licensees may use Column 1 of Table 2 to determine the activity above which instructions must be given to patients. Column 2 provides corresponding dose rates at 1 meter, based on the activities in Column 1. If the patient is breast-feeding an infant or child, additional instructions may be necessary (see Staff Regulatory Guidance 2.2, Additional Instructions for Release of Patients Who Could be Breast-Feeding After Release).

The activities or dose rates in Table 2 may be used for determining when instructions must be given.

When patient-specific calculations (as described in Appendix B) are used, instructions must be provided if the calculation indicates a dose that is greater than 1 millisievert (0.1 rem).

If a radionuclide not listed in Table 2 is administered, the licensee may calculate the activity or dose rate that corresponds to 1 millisievert (0.1 rem). Equation 2 or 3, as appropriate, may be used.

RG 8.39, Rev. 1, Page 9

Table 2. Activities and Dose Rates Above Which Instructions Should be Given When Authorizing Patient Releasea COLUMN 2 COLUMN 1 DOSE RATE AT 1 METER ABOVE ACTIVITY ABOVE WHICH WHICH INSTRUCTIONS ARE INSTRUCTIONS ARE REQUIRED REQUIRED RADIONUCLIDE (GBq) (mCi) (mSv/hr) (mrem/hr)

Ag-111 3.8 100 0.02 2 Au-198 0.69 19 0.04 4 Cr-51 0.96 26 0.004 0.4 Cu-64 1.7 45 0.05 5 Cu-67 2.9 77 0.04 4 Ga-67 1.7 47 0.04 4 I-123 1.2 33 0.05 5 I-125 0.05 1 0.002 0.2 I-125 implant 0.074 2 0.002 0.2 I-131 0.24 7 0.02 2 In-111 0.47 13 0.04 4 Ir-192 implant 0.011 0.3 0.002 0.2 P-32 (b) (b) (b) (b)

Pd-103 implant 0.3 8 0.007 0.7 Re-186 5.7 150 0.03 3 Re-188 5.8 160 0.04 4 Sc-47 2.3 62 0.03 3 Se-75 0.018 0.5 0.001 0.1 Sm-153 5.2 140 0.06 6 Sn-117m 0.21 6 0.009 0.9 Sr-89 (b) (b) (b) (b)

Tc-99m 5.6 150 0.12 12 Tl-201 3.1 85 0.04 4 Y-90 (b) (b) (b) (b)

Yb-169 0.073 2 0.004 0.4

a. The activity values were computed based on 1 millisievert (0.1 rem) total effective dose equivalent.

b. Activity and dose rate limits are not applicable in this case because of the minimal exposures to members of the public resulting from activities normally administered for diagnostic or therapeutic purposes.

NOTES: The millicurie values were calculated using Equations 2 or 3 and the physical half-life. The gigabecquerel values were calculated based on millicurie values and the conversion factor from millicuries to gigabecquerels. The dose rate values were calculated based on millicurie values and exposure rate constants. In general, values are rounded to two significant figures. However, values less than 0.37 gigabecquerel (10 millicuries) or 0.1 millisievert (10 millirems) per hour are rounded to one significant figure. Details of the calculations are provided in NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material (Ref. 2).

Although non-byproduct materials are not regulated by the NRC, information on non-byproduct material is included in this regulatory guide for the convenience of the licensee. Agreement State regulations may vary. Agreement State licensees should check with their State regulations prior to using these values.

RG 8.39, Rev. 1, Page 10

2.2 Additional Instructions for Release of Patients Who Could be Breast-Feeding After Release The requirement in 10 CFR 35.75(b) that a licensee provide instructions including guidance on the discontinuation or the interruption period of breast-feeding, and the potential consequences of failing to follow the recommendation, presumes that the licensee will inquire, as appropriate, regarding the breast-feeding status of the patient. The purpose of the instructions including guidance (e.g., on interruption or discontinuation) is to permit licensees to release a patient who could be breast-feeding an infant or child when the dose to the infant or child could exceed 1 millisievert (0.1 rem) if there is no interruption of breast-feeding.

If the patient could be breast-feeding an infant or child after release, and if the patient was administered a radiopharmaceutical with an activity above the value stated in Column 1 of Table 3, instructions on discontinuation or on the interruption period for breast-feeding and the potential consequences of failing to follow the recommendation must be provided. The patient should also be informed if there would be no consequences to the breast-feeding infant or child. Table 3 also provides recommended duration (column 3) of interrupting or discontinuing breastfeeding to minimize the dose to below 1 millisievert (0.1 rem) if the patient has received certain radiopharmaceutical doses (column 1). The radiopharmaceuticals listed in Table 3 are commonly used in medical diagnosis and treatment.

If a radiopharmaceutical not listed in Table 3 is administered to a patient who could be breast-feeding, the licensee should evaluate whether instructions or records (or both) are required. The dose to the infant or child can be calculated by using the dose conversion factors given for a newborn infant by Stabin (Ref. 5).

If additional instructions are required because the patient is breast-feeding, the instructions should include appropriate recommendations on whether to interrupt breast-feeding, the length of time to interrupt breast-feeding, or, if necessary, the discontinuation of breast-feeding (Ref.6). The instructions should include information on the consequences of failure to follow the recommendation to interrupt or discontinue breastfeeding. The consequences should be explained so that the patient will understand that, in some cases, breastfeeding after an administration of certain radionuclides should be avoided. For example, a consequence of procedures involving I-131 is that continued breastfeeding could harm the infants or childs thyroid.

RG 8.39, Rev. 1, Page 11

Table 3. Activities of Radiopharmaceuticals that Require Instructions and Records When Administered to Patients Who Are Breast-Feeding an Infant or Child COLUMN 1 COLUMN 2 COLUMN 3 ACTIVITY ACTIVITY EXAMPLES OF ABOVE WHICH ABOVE WHICH RECOMMENDED INSTRUCTIONS A RECORD IS DURATION OF ARE REQUIRED REQUIRED INTERRUPTION OF RADIOPHARMACEUTICAL (MBq) (mCi) (MBq) (mCi) BREAST-FEEDINGa I-131 NaI 0.01 0.0004 0.07 0.002 Complete cessation (for this infant or child)

I-123 NaI 20 0.5 100 3 7 days I-123 OIH 100 4 700 20 No interruption I-123 mIBG 70 2 400 10 24 hr for 370 MBq (10 mCi)

I-125 OIH 3 0.08 15 0.4 No Interruption I-131 OIH 10 0.30 60 1.5 Complete cessation (for this infant or child)

Tc-99m DTPA 1,000 30 6,000 150 24 hr Tc-99m MAA 50 1.3 200 24 hr 6

Tc-99m Pertechnetate 100 3 600 15 24 hr Tc-99m DISIDA 1,000 30 6,000 150 24 hr Tc-99m Glucoheptonate 1,000 30 6,000 150 24 hr Tc-99m HAM 400 10 2,000 50 24 hr Tc-99m MIBI 1,000 30 6,000 150 24 hr Tc-99m MDP 1,000 30 6,000 150 24 hr Tc-99m PYP 900 25 4,000 120 24 hr Tc-99m Red Blood Cell In Vivo 400 10 2,000 50 24 hr Labeling Tc-99m Red Blood Cell In Vitro 1,000 30 6,000 150 24 hr Labeling Tc-99m Sulphur Colloid 300 7 1,000 24 hr 30 Tc-99m DTPA Aerosol 1,000 30 6,000 150 24 hr Tc-99m MAG3 1,000 30 6,000 150 24 hr Tc-99m White Blood Cells 100 3 600 15 24 hr Tc-99m Tetrofosmin 24 hr Ga-67 and Zr-80-labeled 1 0.04 7 0.2 28 days Cr-51 EDTA 60 1.6 300 8 No interruption In-111 White Blood Cells 10 0.2 40 1 7 days RG 8.39, Rev. 1, Page 12

Tl-201 Chloride 40 1 200 5 14 days C-11, N-13, O-15, Rb-82 labeled None F-18 labeled 12 hr Lu-177, diagnostic 28 - 35 days Ra-223 and all alpha emitters Complete cessation (for this infant or child)

Ga-55 labeled 12 hr Kr-81m, Xe-133 Gas No interruption Rb-82 Chloride No interruption Zr-89 Antibodies 21 days

a. The duration of interruption of breast-feeding is selected to reduce the maximum dose to a newborn infant to less than 1 millisievert (0.1 rem), although the regulatory limit is 5 millisieverts (0.5 rem). The actual doses that would be received by most infants would be far below 1 millisievert (0.1 rem). The physician may use discretion, recommending increasing or decreasing the duration of interruption, as long as their instructions would result in the dose to the child less than the regulatory limit is 5 millisieverts (0.5 rem).

NOTES: Activities are rounded to one significant figure, except when it was considered appropriate to use two significant figures. Details of the calculations are shown in NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material (Ref. 2). The recommendations in Column 3 of this table are in the Advisory Committee on the Medical Use of Isotopes (ACMUI) Nursing Mother Guidelines for the Medical Administration of Radioactive Materials (Ref. 6) on the interruption or discontinuation of breast-feeding.

Although non-byproduct materials are not regulated by the NRC, information on non-byproduct material is included in this regulatory guide for the convenience of the licensee. Agreement State regulations may vary. Agreement State licensees should check with their State regulations prior to using these values.

2.3 Content of Instructions This section provides licensees with different aspects to consider before and after treatment when developing patient release instructions. Generally, when licensees release patients, it is to the patients home where family or other caregivers may be present. To provide adequate release instructions under 10 CFR 35.75(b), licensees need to consider patient destination upon their release, and the ability of the patient and/or caregiver to understand and follow the release instructions. The licensee should thoroughly ascertain the patient post-treatment destination, and the method they plan to travel there, in order to best estimate the likely cumulative radiation exposures to other members of the public (e.g., family and other caregivers), and thus, direct appropriate protective measures to keep doses ALARA and ensure the dose limit will likely be met.

Iodine-131 (I-131) is the medical radioisotope of highest concern as it is the most commonly used radionuclide in radiopharmaceutical therapy and given its potential for a higher external exposure to members of the public due to its high energy gamma emission and volatility (Ref. 7). However, the regulations in 10 CFR 35.75 apply to other medical radioisotope therapies such as Phosphorus-32 (P-32), Strontium-89 (Sr-89), Yttrium-90 (Y-90), Iodine-125 (I-125), Lutetium-177 (Lu-177), and Radium-223 (Ra-223). None of these radioisotopes have the high energy gamma emission and volatility of I-131, and thus, they present a lower external radiation hazard than I-131. Instructions should be specific to the type of treatment given and should include additional information for individual situations. Note that instructions should not interfere with or contradict the best medical RG 8.39, Rev. 1, Page 13

judgment of physicians. The instructions should include the name of a knowledgeable person to contact and that persons telephone number in case the patient has any questions.

2.3.1 Pre-Treatment Discussions Regarding Radiopharmaceutical Administrations Engaging the patient early in the treatment process (i.e., during treatment planning) may help licensees better familiarize the patient and caregivers with post treatment radiation safety precautions and protective measures, as well as the treatment procedure, potential complications, side effects, dietary and medication changes, pre- and post-treatment expectations.

Additionally, early engagement with the patient affords the patient with the opportunity to ask questions of the licensee that will help the patient be more compliant with the release instructions. It also provides the licensee with the opportunity to determine if the patient will be able to follow the release instructions.

As soon as radiopharmaceutical or implant therapy is considered as a treatment option, the licensee should conduct an interview with the patient and/or caregiver to fully assess the patients specific circumstances. Topics to discuss and consider during the pre-treatment discussion should include:

• Type of post-treatment lodging (e.g., group home, apartment, townhome, detached single family home)

• Patient travel plans to their post-treatment recovery location:

o Will the patient use a private vehicle, taxi service, or public transportation (i.e., bus, train, or airplane)? The use of public transportation should be discouraged, if possible.

o If driving, will the patient be too impaired to drive?

o If driving, will the patient be driving alone (preferred)?

o If the patient is traveling with other individuals, what is the duration of the trip and based on the duration of the trip, can the patient keep an adequate distance from others?

• Household members, if any (gender, age, nursing infant, pregnant woman)

• Can the patient be appropriately isolated from others in the household post-treatment?

• Is the patient capable of self-care, compliance with release instructions, and sleeping alone?

• Is the patient incontinent?

• Are there necessary household or dietary changes (e.g., preexisting medical conditions)?

• Any factors that might be the basis for withholding treatment (e.g., breastfeeding, pregnancy)

• Concerns regarding breastfeeding or pregnancy?

• What consequences would occur if release instructions are not followed?

• Can the patient delay returning to work?

By gathering this information prior to the treatment (i.e., during treatment planning), the licensee can modify assumptions used in their release calculations, as necessary, to provide a patient-specific estimate of the likely cumulative dose to other members of the public; direct appropriate protective measures; and allow the patient time to plan for his/her potential isolation after release.

2.3.2 Patient Precautions RG 8.39, Rev. 1, Page 14

The following precautions/measures should be considered for most patients to minimize exposures to others and keep radiation exposures to others at or below the 5 millisieverts (0.5 rem) limit:

• The licensee should discuss the following precautions and measures with the patient as appropriate. Note: This list is not inclusive and should be modified for each treatment or radioactive material administered.

o Emphasize the importance of keeping an adequate distance from others, especially children and pregnant women. Can arrangements be made for family members (including children and any pregnant household members) to lodge elsewhere temporarily?

o Encourage the patient not to prepare or share food with others.

o Encourage the use of a bathroom reserved exclusively for the patient, if possible.

o Encourage the use of kitchen utensils dedicated to the patient, not shared with other household members and washed separately from other dishes. Alternately, encourage patients to use disposable eating utensils.

o Encourage the use of disposable gloves, flushable wipes, and frequent hand washing.

o Encourage the laundering of a patient's clothing separately from other household members clothing.

o Emphasize abstention from all forms of intimate contact. Advise the patient on the recommended length of time the patient should wait before becoming pregnant to minimize radiation exposures to a developing fetus.

o Discuss how to clean up an area contaminated with body fluids (e.g., breast milk, vomit).

o Emphasize disposing of patient-related trash in a separate plastic bag that is not mixed with other household members' trash, withholding the patient-related trash to allow for radioactive decay, and ways to reduce radiation exposure from this trash. Holding trash for decay is important because the landfill may detect the radiation and send the trash back to the patient.

• Discuss how the patient may contact the licensee if needed.

• Provide post-treatment release instructions to the patient verbally and in writing, including how long the release instructions should be followed.

If the patient, or caregiver, is mentally and/or physically unable to comply with the release instructions provided, licensees may have to consider holding the patient as an inpatient following treatment until the patient can be released without having to follow any specific instructions. Similarly, if the licensee determines that the patients post treatment plans, including any instructions that are believed cannot be followed, planned mode of transportation, and post treatment destination, are likely to cause a dose to another individual that will exceed 5 millisieverts (0.5 rem), the licensee must hold the patient until the dose to other individuals will not exceed 5 millisieverts (0.5 rem).

Information provided in the release instructions may include measures to limit the transfer of radioactive contamination to others. The licensee may encourage patients to have available plastic bags, disposable gloves, and flushable wipes prior to treatment. Specific information on how to limit direct contact with others and measures to limit the contamination of objects, surfaces, and the spread RG 8.39, Rev. 1, Page 15

of radioactive contamination, should be provided. Patient education and awareness of how to minimize, isolate, and clean radioactive contamination is key in minimizing exposure to others.

With regard to female patients of child-bearing age, the NRC recognizes that pregnancy tests have limited ability to detect early pregnancies. The NRC encourages licensees to advise their patients to contact the licensee immediately in instances where a female patient discovers she was pregnant at the time the medical treatment was administered. Licensees must report any dose to an embryo/fetus that is greater than 50 mSv (5 rem) dose equivalent that is a result of the treatment to a pregnant individual unless the dose to the embryo/fetus was specifically approved, in advance, by the authorized user in accordance with 10 CFR 35.3047.

Patients receiving radiopharmaceutical treatment need to be aware that they might trigger the alarms of radiation detectors at national borders, airports, within cities, or at their place of employment for 3 months or more following treatment. Consequently, the licensee may consider issuing the patient a letter or card containing appropriate information about the treatment in case law enforcement agents need to verify that information.

2.3.3 Patient Instructions Licensees must comply with 10 CFR 35.75 by ensuring that the radiation dose to other individuals is not likely to exceed 5 mSv (0.5 rem) from a released patients who have been administered radiopharmaceuticals or permanent implants containing radioactive material. However, once a patient is released, the licensee has no control of the patient. At that point, the patient or caregiver assumes responsibility for managing radiation exposure to other individuals based on the release instructions provided by the licensee. The instructions should be easy to follow so that the patient will understand how to minimize radiation exposure to other individuals (Ref. 8). For most therapies, experience shows that radiation exposure from patients can be safely controlled through appropriate instructions, specific for the treatment, provided by licensees and followed by patients. Below are some instructions that licensees may provide patients post-treatment.

• Wash hands frequently

• Launder clothing separately from others

• Use dedicated or disposable kitchen utensils, and dont share them with others

• Use of a bathroom reserved exclusively for patient, if possible

• Use of disposable gloves and flushable wipes when cleaning

• Disposal of patients trash separately, and hold it to allow for radioactive decay

• Sleep alone

• Abstain from all forms of intimate contact

• Do not prepare or share food with others

• Do not use public transportation, if possible Instructions should be provided to family members and caregivers to notify the treating medical facility of medical emergency or if a patient passes away. Licensee should also inform the patient how to clean up an area contaminated with body fluids (e.g., urine, vomit). Travel arrangements and recovery location should be discussed in detail prior to treatment.

2.3.4 Patient Acknowledgement of Instructions RG 8.39, Rev. 1, Page 16

Prior to release of the patient, the patient should acknowledge receipt of instructions and the licensee should acknowledge the patient understands the instructions as communicated. These acknowledgements could be obtained by using a form signed by both parties. Through the form, the patient acknowledges that he or she:

• Has received a clear explanation of the treatment process.

• Understands the need to limit the exposure to others, especially to young children and pregnant women, and has been informed on how long special care must be exercised.

• Has worked with the healthcare provider to develop plans for:

a) Transportation from the clinic to home or post-treatment destination b) Arrangements for protecting others once arriving at the post-treatment destination c) Minimizing the exposure of people both inside and outside the home d) Managing biological wastes and trash in accordance with NRC, state, and local requirements e) Emergency care f) Whom to contact in the event that questions arise during the recovery period.

2.4 Death of a Patient Following Radiopharmaceutical Administration or Implants In the event that the licensee learns of a patient death while still containing a quantity of radioactive material, the treating medical practitioner and the RSO shall be notified immediately. In cases where the death occurs in a hospital, access to the room occupied by the deceased should be controlled until the room has been decontaminated and surveyed. Radioactive bodies should be identified by a specified form of identifier (e.g., bracelet, badge). Identification of the possibility that a body may contain radioactive material relies on information provided in the patient records, the information card, or information gleaned from relatives or others. A body bag may need to be used to contain the leakage of radioactive material. To minimize external radiation, the body may need to be retained in a secured area. The dose constraints for the pathology staff responsible for the conduct of autopsy examinations will be either those for the general public or those for radiation workers, depending on the training and classification of the staff concerned. These constraints and the radiation safety procedures to be applied in practice should be determined in close consultation with the RSO in which the therapy was administered.

Unsealed radioactive material may be present in a particular body cavity or organ, or they may have concentrated after systemic administration (e.g., I-131 in the thyroid gland). Drainage of the cavity or excision of the organ will reduce exposure if undertaken at the start of the autopsy. In addition, care should be given with respect to organs with significant activity. In cases where the patient had received a dose of beta-emitting colloid or spheres (e.g., P-32 chromic phosphate into a body cavity, Y-90 microspheres into the liver), significant activity may be present in the cavity fluid or in the organ. Beta radiation sources may provide significant dose to the hands because they will be in close contact with body tissues and fluids (Ref. 9).

Autopsy and pathology staff should wear standard protective clothing (i.e., gloves, lab coats, eye protection) and personnel monitoring should be considered. For beta emitters, double surgical gloves may be helpful in reducing skin exposures. An intake of airborne material inadvertently released during cutting or movement of radioactive tissue or organs can be prevented by wearing a face shield, or eye protection and a face mask. A proportion of the activity retained will appear in cremated remains and may be a concern, particularly in the case of long lived radionuclides, to require controls to be specified. The main RG 8.39, Rev. 1, Page 17

concern is in respect to the scattering of ashes, although contact dose rates with the container may have to be considered if cremation takes place shortly after administration.

Crematorium employees may receive external exposure from the radioactive body or from contamination of the crematorium or internal exposure from inhalation of radioactive particles while handling the ashes.

Bodies that contain gamma emitting radionuclides will result in some external exposure to crematorium employees. Cremation of non-volatile radionuclides might result in contamination of the furnace. As there is a potential for inhalation of contaminated ash particles during cleaning of the furnace, it is appropriate for workers who clean the furnace to wear dust masks and protective garments. The most likely hazard to the general population in the vicinity of the crematorium is the inhalation of radioactive material emitted with the stack gases. Each crematorium should maintain records of the type and activity in bodies cremated, when known (Ref. 9).

The RSO should be consulted to determine the amount of activity remaining in the deceased patient. No special precautions are required, provided that the activity remaining in the corpse is not in excess of the applicable regulatory limits.

• If the activity remaining in the body is greater than regulatory limits, or if regulatory limits have not been established, the RSO should determine the radiation precautions to be followed.

• Precautions should be based on dose limits, a generic safety assessment of the need for monitoring personnel who carry out these procedures, the need for monitoring the premises, the need for minimizing external radiation exposure, and the potential for contamination (Ref. 9).

2.5 Precautions for Long-lived Contaminants in Radiopharmaceutical Therapy With certain radionuclides used in radiopharmaceutical therapy, there is the potential for long-lived contaminants to be present from radioactive decay. As advances in radiopharmaceutical therapy result in the use of new radionuclides, licensees need to consider the radioactive emissions from the contaminants that may be present, and their half-life when release instructions are prepared for patients (Ref. 10).

3. Records 3.1 Records of Release There is no requirement for recordkeeping on the release of patients who were released in accordance with Column 1 of Table 1. However, if the release of the patient is based on a dose calculation that considered retained activity, an occupancy factor less than 0.25 at 1 meter, effective half- life, or shielding by tissue, a record of the basis for the release is required by 10 CFR 35.75(c). This record should include the patient identifier (in a way that ensures that confidential patient information is not traceable or attributable to a specific patient), the radioactive material administered, the administered activity, and the date of the administration. In addition, depending on the basis for release, records should include the following information.

1. For Immediate Release of a Patient Based on a Patient-Specific Calculation: The equation used, including the patient-specific factors and their bases that were used in calculating the dose to the person exposed to the patient, and the calculated dose. The patient-specific factors (see Appendix B of this guide) include the effective half-life and uptake fraction for each component of the biokinetic model, the time that the physical hal-life was RG 8.39, Rev. 1, Page 18

assumed to apply to retention, and the occupancy factor. The basis for selecting each of these values should be included in the record.

2. For Immediate Release of a Patient Based on Measured Dose Rate: The results of the measurement, the specific survey instrument used, and the name of the individual performing the survey.

3. For Delayed Release of a Patient Based on Radioactive Decay Calculation: The time of the administration, date and time of release, and the results of the decay calculation.

4. For Delayed Release of a Patient Based on Measured Dose Rate: The results of the survey meter measurement, the specific survey instrument used, and the name of the individual performing the survey.

In some situations, a calculation may be case-specific for a class of patients who all have the same patient-specific factors. In this case, the record for a particular patients release may reference the calculation for the class of patients.

Records, as required by 10 CFR 35.75(c), should be kept in a manner that ensures the patients confidentiality, that is, the records should not contain the patients name or any other information that could lead to identification of the patient. These recordkeeping requirements may also be used to verify that licensees have proper procedures in place for assessing potential third-party exposure associated with and arising from exposure to patients administered radioactive material.

3.2 Records of Instructions for Breast-Feeding Patients If failure to interrupt or discontinue breast-feeding could result in a dose to the infant or child in excess of 5 millisievert (0.5 rem), a record that instructions were provided is required by 10 CFR 35.75(d).

Column 2 of Table 3 states, for the radiopharmaceuticals commonly used in medical diagnosis and treatment, the activities that would require such records when administered to patients who are breast-feeding.

The record should include the patients identifier (in a way that ensures that confidential patient information is not traceable or attributable to a specific patient), the radiopharmaceutical administered, the administered activity, the date of the administration, and whether instructions were provided to the patient who could be breast-feeding an infant or child.

4 Summary Table Table 4 summarizes the criteria for releasing patients and the requirements for providing instructions and maintaining records.

RG 8.39, Rev. 1, Page 19

Table 4. Summary of Release Criteria, Required Instructions to Patients, and Records to be Maintained PATIENT BASIS FOR CRITERIA FOR INSTRUCTIONS RELEASE RECORDS GROUP RELEASE RELEASE NEEDED? REQUIRED?

Administered Administered Yes - if administered No activity activity Column activity 1 of Table 1 > Column 1 of Table 2 All patients, including Retained activity Retained activity Yes - if retained Yes patients who are breast-feeding Column 1 of activity an infant or Table 1 > Column 1 of Table 2 child Measured dose Measured dose rate Yes - if dose rate > Yes rate Column 2 of Column 2 of Table 2 Table 1 Patient-specific Calculated dose Yes - if calculated dose Yes calculations 5 mSv (0.5 rem) > 1 mSv (0.1 rem)

Patients who All the above Additional instructions Records that are breast- bases for required if: instructions were feeding an release provided if:

Administered activity infant or

> Column 1 of Table 3 Administered activity child or > Column 2 of Table Licensee calculated 3 dose from breast- or feeding > 1 mSv Licensee calculated (0.1 rem) to the infant dose from continued or child breast-feeding > 5 mSv (0.5 rem) to the infant or child RG 8.39, Rev. 1, Page 20

D. IMPLEMENTATION The purpose of this section is to provide information to applicants and licensees regarding the NRCs plans for using this regulatory guide.

Use by Applicants and Licensees Applicants and licensees may voluntarily use the guidance in this document to demonstrate compliance with the NRC regulations. Methods or solutions that differ from those described or referenced in this regulatory guide may be deemed acceptable if they provide sufficient basis and information for the NRC staff to verify that the proposed alternative demonstrates compliance with the appropriate NRC regulations.

Licensees may use the information in this regulatory guide for actions that do not require NRC review and approval. Licensees may use the information in this regulatory guide or applicable parts to resolve regulatory or inspection issues.

Use by NRC Staff The NRC staff does not intend or approve any imposition of the guidance in this regulatory guide. The NRC staff does not expect any existing licensee to use or commit to using the guidance in this regulatory guide, unless the licensee makes a change to its licensing basis. The NRC staff does not expect or plan to request licensees to voluntarily adopt this regulatory guide to resolve a generic regulatory issue. The NRC staff does not expect or plan to initiate NRC regulatory action that would require the use of this regulatory guide. Examples of such unplanned NRC regulatory actions include issuance of an order, generic communication, or rule requiring the use of this regulatory guide.

The staff may discuss with licensees various actions consistent with staff positions in this regulatory guide, as one acceptable means of meeting the NRC regulatory requirement. However, unless this regulatory guide is part of the licensing basis for a facility, the staff may not represent to the licensee that the licensees failure to comply with the positions in this regulatory guide constitutes a violation.

If an existing licensee voluntarily seeks a license amendment or change and (1) the NRC staffs consideration of the request involves a regulatory issue directly relevant to this regulatory guide, and (2) the specific subject matter of this regulatory guide is an essential consideration in the staffs determination of the acceptability of the licensees request, then the staff may request that the licensee either follow the guidance in this regulatory guide or provide an equivalent alternative process that demonstrates compliance with the NRC regulatory requirements.

RG 8.39, Rev. 1, Page 21

REFERENCES

1. Code of Federal Regulations, Medical Use of Byproduct Material, Part 35, Chapter I, Title 10.

2. U.S. Nuclear Regulatory Commission, Consolidated Guidance About Materials Licenses: Program-Specific Guidance About Medical Use Licenses, NUREG-1556, Volume 9, Washington, DC 20555, 2008.

3. U.S. Nuclear Regulatory Commission, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material, NUREG-1492, Washington, DC 20555, 1997.

4. National Council on Radiation Protection and Measurements (NCRP), NCRP Report 37, Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides, Bethesda, MD 1970.

5. Stabin, M., Internal Dosimetry in Pediatric Nuclear Medicine, Pediatric Nuclear Medicine, Edited by S. Treves, Springer Verlag, New York, p. 556 - 581, 1995.

6. Advisory Committee on the Medical Uses of Isotopes (ACMUI), Nursing Mother Guidelines for the Medical Administration of Radioactive Materials, 2018, Agencywide Documents Access and Management System (ADAMS) Accession No. ML18177A451.

7. U.S. Nuclear Regulatory Commission, Staff Evaluation of the U.S. Nuclear Regulatory Commission's Program Regulating Patient Release After Radioisotope Therapy, SECY 0015, Washington, DC 20555, 2018, Agencywide Documents Access and Management System (ADAMS) Accession No. ML17279B139.

8. Advisory Committee on the Medical Uses of Isotopes (ACMUI), Patient Release Report, 2010, Agencywide Documents Access and Management System (ADAMS) Accession No. ML103481099.

9. National Council on Radiation Protection and Measurements (NCRP), NCRP Report 155, Management of Radionuclide Therapy Patients, Bethesda, MD 2006.

10. U.S. Nuclear Regulatory Commission, Licensing of Lutetium-177, Memorandum to the NRC Regions, June, 2018, Agencywide Documents Access and Management System (ADAMS) Accession No. ML18136A824.

RG 8.39, Rev. 1, Page 22

APPENDIX A Table A-1. Half-Lives and Exposure Rate Constants of Radionuclides Used in Medicine EXPOSURE EXPOSURE RATE RATE HALF- CONSTANTb HALF- CONSTANTb LIFE (R/mCi-h LIFE (R/mCi-h at 1 RADIONUCLIDE (DAYS)a at 1 cm) RADIONUCLIDE (DAYS)a cm)

Ag-111 7.45 0.150 Pd-103 implant 16.96 0.86d Au-198 2.696 2.3 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 3.351 0.56 Cu-67 2.578 0.58 Se-75 119.8 2.0 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 NAe I-125 implant 60.14 1.11c Tc-99m 0.251 0.756 I-131 8.04 2.2 TI-201 3.044 0.447 In-111 2.83 3.21 Y-90 2.67 NAe Ir-192 implant 74.02 4.594 Yb-169 32.01 1.83 P-32 14.29 NAe

a. K. F. Eckerman, A. B. Wolbarst, and A. C. B. Richardson, Federal Guidance Report No. 11, Limiting Values of Radionuclide Intake and Air Concentration and Dose Conversion Factors for Inhalation, Submersion, and Ingestion, Report No. EPA-520/1-88-020, Office of Radiation Programs, U.S. Environmental Protection Agency, Washington, DC, 1988.

b. Values for the exposure rate constant for Au-198, Cr-51, Cu-64, I-131, Sc-47, and Se-75 were taken from the Radiological Health Handbook, U.S. Department of Health, Education, and Welfare, pg. 135, 1970. For Cu- 67,1-123, In-111, Re-186, and Re-188, the values for the exposure rate constant were taken from D. E. Barber, J. W.

Baum, and C. B. Meinhold, Radiation Safety Issues Related to Radiolabeled Antibodies, NUREG/CR-4444, U.S.

NRC, Washington, DC, 1991. For Ag-111, Ga-67, I-125, Sm-153, Sn-117m, Tc- 99m, T1-201, and Yb-169, the exposure rate constants were calculated because the published values for these radionuclides were an approximation, presented as a range, or varied from one reference to another. Details of the calculation of the exposure rate constants are shown in Table A.2 of Appendix A to NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material, U.S. NRC, February 1997.

c. R. Nath, A. S. Meigooni, and J. A. Meli, Dosimetry on Transverse Axes of 125I and 192Ir 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.

d. A. S. Meigooni S. Sabnis, R. Nath, Dosimetry of Palladium-103 Brachytherapy Sources for Permanent Implants, Endocurietherapy Hyperthermia Oncology, 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.

e. Not applicable (NA) because the release activity is not based on beta emissions.

Appendix A to RG-8.39, Page A-1

APPENDIX B PROCEDURES FOR CALCULATING DOSES BASED ON PATIENT-SPECIFIC FACTORS A licensee may release a patient who has been administered an activity higher than the values listed in Column 1 of Table 1 of this regulatory guide if dose calculations using patient-specific parameters, which are less conservative than the conservative assumptions, show that the potential total effective dose equivalent to any individual would be no greater than 5 millisieverts (0.5 rem).

If the release of a patient is based on a patient-specific calculation that considered retained activity, an occupancy factor less than 0.25 at 1 meter, effective half-life, or shielding by tissue, a record of the basis of the release is required by 10 CFR 35.75(c).

The following equation can be used to calculate doses:

0.693t / Tp 34.6 Q0 TE (1 e )

D(t) = (Equation B-1) r2 Where D(t) = Accumulated dose to time t, in rems 34.6 = Conversion factor of 24 hrs/day times total integration of decay (1.44)

F = Exposure rate constant for a point source, R/mCi x hr at 1 cm Q0 = Initial activity at the start of the time interval Tp = Physical half-life in days E = Occupancy factor that accounts for different occupancy times and distances when an individual is around a patient r = Distance in centimeters (this value is typically 100 cm) t = exposure time in days B-1. Occupancy Factor B-1.1 Rationale for Occupancy Factors Used to Derive Table 1 In Table 1 in this regulatory guide, the activities at which patients could be released were calculated using the physical half-life of the radionuclide and an occupancy factor at 1 meter of either 0.25 (if the radionuclide has a half-life longer than 1 day) or 1.0 (if the radionuclide has a half-life less than or equal to 1 day). The basis for the occupancy factor of 0.25 at 1 meter is that measurements of doses to family members as well as considerations of normal human behavior (as discussed in the supporting regulatory analysis (Ref. B-1)) suggest that an occupancy factor of 0.25 at 1 meter, when used in combination with the physical half-life, will produce a generally conservative estimate of the dose to family members when instructions on minimizing doses to others are given.

An occupancy factor of 0.25 at 1 meter is not considered appropriate when the physical half-life is less Appendix B to RG-8.39, Page B-1

than or equal to 1 day, and hence, the dose is delivered over a short time. Specifically, the assumptions regarding patient behavior that led to an occupancy factor of 0.25 at 1 meter include the assumption that the patient will not be in close proximity to other individuals for several days. However, when the dose is from a short-lived radionuclide, the time that individuals spend in close proximity to the patient immediately following release will be most significant because the dose to other individuals could be a large fraction of the total dose from the short-lived radionuclide. Thus, to be conservative when providing generally applicable release quantities that may be used with little consideration of the specific details of a particular patients release, the values calculated in Table I were based on an occupancy factor of 1 at 1 meter when the half-life is less than or equal to 1 day.

B-1.2 Occupancy Factors to Consider for Patient-Specific Calculations The selection of an occupancy factor for patient-specific calculations will depend on whether the physical or effective half-life of the radionuclide is used and whether instructions are provided to the patient before release. The following occupancy factors, E, at 1 meter, may be used for patient-specific calculations.

• E = 0.75 when a physical half-life, an effective half-life, or a specific time period under consideration (e.g., bladder holding time) is less than or equal to 1 day.

• E = 0.25 when an effective half-life is greater than 1 day if the patient has been given instructions, such as,

- Maintain a prudent distance from others for at least the first 2 days,

- Sleep alone in a room for at least the first night,

- Do not travel by airplane or mass transportation for at least the first day,

- Do not travel on a prolonged automobile trip with others for at least the first 2 days,

- Have sole use of a bathroom for at least the first 2 days, and

- Drink plenty of fluids for at least the first 2 days.

• E = 0.125 when an effective half-life is greater than 1 day if the patient has been given instructions, such as,

- Follow the instructions for E = 0.25 above,

- Live alone for at least the first 2 days, and

- Have few visits by family or friends for at least the first 2 days.

• In a two-component model (e.g., uptake of I-131 using thyroidal and extrathyroidal components), if the effective half-life associated with one component is less than or equal to one day but is greater than one day for the other component, it is more justifiable to use the occupancy factor associated with the dominant component for both components.

Example 1: Calculate the maximum likely dose to an individual exposed to a patient who has received 2,220 megabecquerels (60 millicuries) of I-131. The patient has been provided with instructions to maintain a prudent distance from others for at least 2 days, lives alone, drives home alone, and stays at home for several days without visitors.

Appendix B to RG-8.39, Page B-2

Solution: The dose to total decay (t = ) is calculated based on the physical half-life using Equation B-1.

(This calculation illustrates the use of physical half-life. To account for biological elimination, calculations described in the next section should be used.)

34.6

() =

r2 Since the patient has been provided with instructions for reducing exposure as recommended for an occupancy factor of E = 0.125, the occupancy factor of 0.125 at 1 meter may be used.

2 34.6 2.2 (8.04)(0.125)

() =

(100 cm)2

() = 4.59 (0.459 )

Since the dose is less than 5 millisieverts (0.5 rem), the patient may be released, but 10 CFR 35.75(b) requires that instructions be given to the patient on maintaining doses to others ALARA. A record of the calculation must be maintained pursuant to 10 CFR 35.75(c) because an occupancy factor less than 0.25 at 1 meter was used.

B-2. Effective Half-Life A licensee may take into account the effective half-life of the radioactive material to demonstrate compliance with the dose limits for individuals exposed to the patient that are stated in 10 CFR 35.75.

The effective half-life is defined as:

= +

(Equation B-2)

Where Tb = biological half-life of the radionuclide Tp = physical half-life of the radionuclide.

The behavior of I-131 can be modeled using two components: extrathyroidal iodide (i.e., existing outside of the thyroid) and thyroidal iodide following uptake by the thyroid. The effective half- lives for the extrathyroidal and thyroidal fractions (F1 and F2, respectively) can be calculated with the following equations:

1 1 = 1 +

(Equation B-3)

Appendix B to RG-8.39, Page B-3

2 2 = (Equation B-4) 2 +

Tb1 = biological half-life for extrathyroidal iodide Tb2 = biological half-life of iodide following uptake by the thyroid Tp = physical half-life of I-131.

However, simple exponential excretion models do not account for (a) the time for the I-131 to be absorbed from the stomach to the blood and (b) the holdup of iodine in the urine while in the bladder.

Failure to account for these factors could result in an underestimate of the dose to another individual.

Therefore, this guide makes a conservative approximation to account for these factors by assuming that, during the first 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> after the administration, about 80 percent of the I-131 administered is removed from the body at a rate determined only by the physical half-life of I-131.

Thus, an equation to calculate the dose from a patient administered I-131 may have three components. The first component is the dose for the first 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> (0.33 day) after administration. This component comes directly from Equation B-1 using the physical half-life and a factor of 80 percent. The second component is the dose from the extrathyroidal component from 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> to total decay. In this component, the first exponential factor represents the activity at t = 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> based on the physical half-life of I-131. The second exponential factor represents the activity from t = 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> to total decay based on the effective half-life of the extrathyroidal component. The third component, the dose from the thyroidal component for 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> to total decay, is calculated in the same manner as the second component. The full equation is shown as Equation B-5.

0.693(0.33) 34.6 1 (0.8) 1

+

() = (Equation B-5)

(100 cm)2 0.693(0.33)/ 0.693(0.33)/

2 1 1 + 2 2 2 F1 = Extrathyroidal uptake fraction F2 = Thyroidal uptake fraction El = Occupancy factor for the first 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> E2 = Occupancy factor from 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> to total decay.

All the other parameters are as defined in Equations B-1, B-3, and B-4. Acceptable values for F1, T1eff, F2, and T2eff are shown in Table B-1 for thyroid ablation and treatment of thyroid remnants after surgical removal of the thyroid for thyroid cancer. If these values have been measured for a specific individual, the measured values may be used.

The record of the patients release required by 10 CFR 35.75(c) is described in Regulatory Position 3.1 of this guide.

Example 2, Thyroid Cancer: Calculate the maximum likely dose to an individual exposed to a patient who has been administered 7,400 megabecquerels (200 millicuries) of I-131 for the treatment of thyroid remnants and metastases.

Appendix B to RG-8.39, Page B-4

Solution: In this example, we will calculate the dose by using Equation B-5 to account for the elimination of I-131 from the body, based on the effective half-lives appropriate for thyroid cancer. The physical half-life and the exposure rate constant are from Table A-1. The uptake fractions and effective half-lives are from Table B-1. An occupancy factor, E, of 0.75 at 1 meter will be used for the first component because the time period under consideration is less than 1 day. However, for the second and third components, an occupancy factor of 0.25 will be used because (1) the effective half-life associated with the dominant component is greater than 1 day and (2) patient-specific questions were provided to the patient to justify the occupancy factor (see Section B.1.2, Occupancy Factors to Consider for Patient-Specific Calculations, of this appendix).

Table B-1. Uptake Fractions and Effective Half-Lives for Iodine-131 Treatments Extrathyroidal Component Thyroidal Component Uptake Fraction Effective Half-Life Uptake Fraction Effective Half-Life Medical Condition F1 T1eff (day) F2 T2eff (day)

Hyperthyroidism 0.20a 0.32b 0.80a 5.2a Postthyroidectomy 0.95c 0.32b 0.05c 7.3b for Thyroid Cancer

a. M. G. Stabin et al., Radiation Dosimetry for the Adult Female and Fetus from Iodine-131 Administration in Hyperthyroidism, Journal of Nuclear Medicine, Volume 32, Number 5, May 1991. The thyroid uptake fraction of 0.80 was selected as one that is seldom exceeded by the data shown in Figure 1 in this referenced document.

The effective half-life of 5.2 days for the thyroidal component was derived from a biological half- life of 15 days, which was obtained from a straight-line fit that accounts for about 75 percent of the data points shown in Figure 1 of this Journal of Nuclear Medicine document.

b. International Commission on Radiological Protection (ICRP), Radiation Dose to Patients from Radiopharmaceuticals, ICRP Publication No. 53, March 1987. (Available for sale from Pergamon Press, Inc., Elmsford, NY 10523.) The data in this ICRP document suggest that the extrathyroidal component effective half-life in normal subjects is about 0.32 days. Lacking other data, this value is applied to hyperthyroid and thyroid cancer patients. For thyroid cancer, the thyroidal component effective half-life of 7.3 days is based on a biological half-life of 80 days (adult thyroid) as suggested in this ICRP document.

c. The thyroidal uptake fraction of 0.05 was recommended by Dr. M. Pollycove, M.D., NRC medical visiting fellow, as an upper limit postthyroidectomy for thyroid cancer.

Substituting the appropriate values into Equation B-5, the dose to total decay is 34.6 (2.2)(200) 0.693(0.33) 0.693(0.33)

() = 2 (0.75)(8.04)(0.8) 1 8.04 + 8.04 (0.25)(0.95)(0.32)

(100 cm) 0.693(0.33)

+ 8.04 (0.25)(0.05)(7.3)

D() = 4.53 millisieverts (0.453 rem)

Appendix B to RG-8.39, Page B-5

Therefore, thyroid cancer patients administered 7,400 megabecquerels (200 millicuries) of I-131 or less would not have to remain under licensee control and could be released under 10 CFR 35.75, assuming that the foregoing assumptions can be justified for the individual patients case and that the patient is given instructions. Patients administered somewhat larger activities could also be released immediately if the dose is not greater than 5 millisieverts (0.5 rem).

In the example above, the thyroidal fraction, F2 = 0.05, is a conservative assumption for persons who have had surgery to remove thyroidal tissue. If F2 has been measured for a specific patient, the measured value may be used.

Example 3, Hyperthyroidism: Calculate the maximum likely dose to an individual exposed to a patient who has been administered 2,035 megabecquerels (55 millicuries) of I-131 for the treatment of hyperthyroidism (i.e., thyroid ablation).

Solution: In this example, we will again calculate the dose using Equation B-5, Table A-1, and Table B-1 to account for the elimination of I-131 from the body by using the effective half-lives appropriate for hyperthyroidism. An occupancy factor, E, of 0.25 at 1 meter will be used for the second and third components of the equation because patient-specific instructions were provided to justify the occupancy factor (see Section B.1.2, Occupancy Factors To Consider for Patient-Specific Calculations).

Substituting the appropriate values into Equation B-5, the dose to total decay is 34.6 (2.2)(55) 0.693(0.33)

() = 2 (0.75)(8.04)(0.8) 1 8.04 (100 cm) 0.693(0.33)

+ 8.04 (0.25)(0.20)(0.32) 0.693(0.33)

+ 8.04 (0.25)(0.80)(5.2)

D() = 4.86mSv (0.486 rem)

Therefore, hyperthyroid patients administered 2,035 megabecquerels (55 millicuries) of I-131 would not have to remain under licensee control and could be released under 10 CFR 35.75 when the occupancy factor of 0.25 in the second and third components of the equation is justified.

In the example above, the thyroidal fraction, F2 = 0.8, is a conservative assumption for persons who have this treatment for hyperthyroidism. If F2 has been measured for a specific patient, the measured value may be used.

B-3. Internal Dose For some radionuclides, such as I-131, there may be concerns that the internal dose of an individual from exposure to a released patient could be significant. A rough estimate of the maximum likely committed effective dose equivalent from internal exposure can be calculated from Equation B-6.

Di = Q (10-5)(DCF) (Equation B-6)

Appendix B to RG-8.39, Page B-6

Where Di = Maximum likely internal committed effective dose equivalent to the individual exposed to the patient in rems Q = Activity administered to the patient in millicuries 10-5 = Assumed fractional intake DCF = Dose conversion factor to convert an intake in millicuries to an internal committed effective dose equivalent (such as tabulated in Reference B-2).

Equation B-6 uses a value of 10-5 as the fraction of the activity administered to the patient that would be taken in by the individual exposed to the patient. A common rule of thumb is to assume that no more than 1 millionth of the activity being handled will become an intake to an individual working with the material.

This rule of thumb was developed in Reference B-3 for cases of worker intakes during normal workplace operations, worker intakes from accidental exposures, and public intakes from accidental airborne releases from a facility, but it does not specifically apply for cases of intake by an individual exposed to a patient.

However, two studies (Refs. B-4 and B-5) regarding the intakes of individuals exposed to patients administered I-131 indicated that intakes were generally of the order of 1 millionth of the activity administered to the patient and that internal doses were far below external doses. To account for the most highly exposed individual and to add a degree of conservatism to the calculations, a fractional transfer of 10-5 has been assumed.

Example 4, Internal Dose: Using the ingestion pathway, calculate the maximum internal dose to a person exposed to a patient who has been administered 1,110 megabecquerels (33 millicuries) of I-131. The ingestion pathway was selected since it is likely that most of the intake would be through the mouth or through the skin, which is most closely approximated by the ingestion pathway.

Solution: This is an example of the use of Equation B-6. The dose conversion factor DCF for the ingestion pathway is 53 rems/millicurie from Table 2.2 of Reference B-2.

Substituting the appropriate values into Equation B-6, the maximum internal dose to the person is Di = (33 mCi)(10-5)(53 rem/mCi)

Di = 0.17 mSv (0.017 rem)

In this case, the external dose to the other person would be no greater than 5 millisieverts (0.5 rem), while the internal dose would be about 0.17 millisievert (0.017 rem). Thus, the internal dose is about 3 percent of the external gamma dose. Internal doses may be ignored in the calculations if they are likely to be less than 10 percent of the external dose since the internal dose would be significantly less than the uncertainty in the external dose.

The conclusion that internal contamination is relatively unimportant in the case of patient release was also reached by the NCRP. The NCRP addressed the risk of intake of radionuclides from patients secretions and excreta in NCRP Commentary No. 11, Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients (Ref. B-6). The NCRP concluded, Thus, a contamination incident that could lead to a significant intake of radioactive material is very unlikely. For additional discussion on the subject, see Reference B-1.

Appendix B to RG-8.39, Page B-7

REFERENCES FOR APPENDIX B B-1. U.S. Nuclear Regulatory Commission, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material, NUREG-1492, Washington, DC 20555, 1997. 1 B-2. K. F. Eckerman, A. B. Wolbarst, and A. C. B. Richardson, Limiting Values of Radionuclide Intake and Air Concentration and Dose Conversion Factors for Inhalation, Submersion, and Ingestion, Federal Guidance Report No. 11, U. S. Environmental Protection Agency, Washington, DC, 1988.

B-3. A. Brodsky, Resuspension Factors and Probabilities of Intake of Material in Process (or Is 10-6 a Magic Number in Health Physics?), Health Physics, Volume 39, Number 6, 1980.

B-4. R. C. T. Buchanan and J. M. Brindle, Radioiodine Therapy to Out-patients-The Contamination Hazard, British Journal of Radiology, Volume 43, 1970.

B-5. A. P. Jacobson, P. A. Plato, and D. Toeroek, Contamination of the Home Environment by Patients Treated with Iodine-131, American Journal of Public Health, Volume 68, Number 3, 1978.

B-6. National Council on Radiation Protection and Measurements, Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients, Commentary No. 11, February 28, 1995.

1 Copies may be purchased at current rates from the U.S. Government Printing Office, P. 0. Box 37082, Washington, DC 20402-9328 (telephone (202) 512-2249; or from the National Technical Information service by writing NTIS at 5285 Port Royal Road, Springfield, VA 22161. Copies of drafts are also available for inspection and copying for a fee from the NRC Public Document Room at 2120 L Street NW. (Lower Level), Washington, DC. The PDRs mailing address is Mail Stop LL-6, Washington, DC 20555; telephone (202) 634-3273; fax (202) 634- 3343.

Appendix B to RG-8.39, Page B-8