THE UNIVERSITY OF NEW MEXICOHEALTH SCIENCES CENTER

COLLEGE OF PHARMACYALBUQUERQUE, NEW MEXICO

Correspondence Continuing Education Coursesfor

Nuclear Pharmacists and Nuclear MedicineProfessionals

VOLUME IX, NUMBER 1

Current Practice for the Release of PatientsAdministered Radioactive Materials

By:

Steven G. Marsh, MSThe Ohio State University Medical Center,

Columbus, OHand

Robert E. Reiman, MDDuke University Medical Center,

Durham, NC

The University of New Mexico Health Sciences Center College of Pharmacy is approved by theAmerican Council on Pharmaceutical Education as a provider of continuing pharmaceuticaleducation. Program No. 039-000-01-002-H04. 2.5 Contact Hours or .25 CEUs.

Current Practice for the Release of PatientsAdministered Radioactive Materials

By:

Steven G. Marsh, MSRobert E. Reiman, MD

Coordinating Editor and Director of Pharmacy Continuing EducationWilliam B. Hladik III, MS, RPh

College of PharmacyUniversity of New Mexico Health Sciences Center

Managing EditorJulliana Newman, ELS

Wellman Publishing, Inc.Albuquerque, New Mexico

Editorial BoardGeorge H. Hinkle, MS, RPh, BCNP

William B. Hladik III, MS, RPhJeffrey P. Norenberg, MS, RPh, BCNP

Laura L. Boles Ponto, PhD, RPhTimothy M. Quinton, PharmD, MS, RPh, BCNP

Guest ReviewerJeffry A. Siegel, PhD

President & CEONuclear Physics Enterprises

216 Society HillCherry Hill, NJ 08003

While the advice and information in this publication are believed to be true and accurate at press time, the author(s),editors, or the publisher cannot accept any legal responsibility for any error or ommissions that may be made. The

publisher makes no warranty, express or implied, with respect to the material contained herein.

Copyright 2001University of New Mexico Health Sciences Center

Pharmacy Continuing EducationAlbuquerque, New Mexico

CURRENT PRACTICE FOR THE RELEASE OF PATIENTS

ADMINISTERED RADIOACTIVE MATERIALS

STATEMENT OF OBJECTIVES

The purpose of this continuing education lesson is to increase the reader’s knowledge and

understanding of the newly adopted Nuclear Regulatory Commission guidelines for the release

of patients who have been administered radioactive material.

On completion of this material, the reader should be able to:

1. Describe the 1997 NRC regulations for the diagnostic and therapeutic uses of

radionuclides in accordance with release criteria as stated in 10 CFR 35.75.

2. Describe methods for demonstrating compliance with 10 CFR 35.75 regulations.

3. Discuss advantages/disadvantages of the new “dose-based” limits.

4. Discuss the four criteria used in the release of patients administered radioactive

materials.

5. Describe and discuss calculaion methods and asumptions for the release of patients

based on administered radioacivity and patient specific dose calculations.

6. Describe and discuss four criteria for instructions.

7. Describe and discuss content of written instructions.

8. Describe and discuss records of release and minimum information required.

COURSE OUTLINE

I. INTRODUCTION

II. THE CHANGING REGULATORYCLIMATE

III. NRC REVISED REGULATION10 CFR 35.75

IV. HOW LICENSEES CANIMPLEMENT THE NEWREGULATIONS

A. Criteria Used for the Release ofPatients Administered RadioactiveMaterial

B. Required Instructions

C. Maintenance of Required Records

D. Computation of Dose to ExposedIndividual

V. PRACTICAL APPLICATION OFTHE CRITERIA

VI. EXAMPLES

VII. DISCUSION

VIII.REFERENCES

IX. QUESTIONS

1

CURRENT PRACTICE FOR THERELEASE OF PATIENTS

ADMINISTERED RADIOACTIVEMATERIALS

By:Steven G. Marsh, MS, and

Robert E. Reiman, MDFrom the Ohio State University Medical

Center (Marsh), Columbus, OH, and DukeUniversity Medical Center (Reiman),

Durham, NC.

INTRODUCTIONRadiopharmaceuticals are unique

among therapeutic agents in that they do notlimit their effects to the patient undergoingtreatment, but may directly affect the healthand safety of individuals who associate withthe patient. For example, a patient beingtreated with radioiodine for thyroid carcinomamay expose family members, friends,coworkers and other members of the publicto both gamma radiation and to radioactivecontamination that is excreted in urine, per-spiration and saliva. For many years, treat-ment with radiopharmaceuticals requiredhospitalization of the patient until theretained radioactivity decreased to certainacceptable levels. In 1997, new risk-informed rules were implemented by theUnited States Nuclear RegulatoryCommission (NRC), which significantlymodified the conditions under which patientswere required to remain in medical isolation.

Because radiopharmacists and othernuclear medicine professionals will beinvolved in counseling patients and familieswith regard to the precautions that are sug-gested following release from medical isola-tion, it is important that they become familiarwith the rationale for the precautions, and theways in which they are implemented. In thislesson, we will (a) review the regulatorybasis for the release of patients, (b) reviewthe ways in which the NRC expects licensees

to comply with the new regulatory guidance,(c) demonstrate ways in which licensees cancomply with the requirements and (d) presentevidence that the new release regulations areeffective in reducing radiation exposure toindividuals to acceptable levels.

THE CHANGING REGULATORYCLIMATE

Regulations governing the release ofpatients who receive radiopharmaceuticalsfrom medical isolation or confinement wereimplemented because of concerns regardingstochastic radiogenic risks for those individ-uals exposed to such patients. These risksinclude carcinogenesis and germ cell muta-genesis. These regulations, which remainedin effect until 1997, established the retained-activity limit for patient release for 131I of30 mCi (or a maximum dose rate of 5 mremper hour at one meter) in the United States.

The development of new radiophar-maceuticals for therapy, along with the goalof optimizing clinical efficacy, cost-effec-tiveness and accessibility, led to an effort todevelop regulations based on sound dosimet-ric and radiobiological principles. The origi-nal 30 mCi limit for 131I proved to be a rea-sonable value based on actual measurementsof exposure rates in the proximity of hyper-thyroid patients following 131I treatment.These measurements indicated that an aver-age retained activity of 29 mCi yields aneffective dose of 0.5 rem to family mem-bers.1-3 This result was based on an assump-tion of complete in vivo physical decay withno biological elimination of the radioactivity.Although these assumptions may be appro-priate for patients who have an intact thyroid,they are not valid in post-thyroidectomypatients being treated for metastatic thyroidcancer, who characteristically have relativelylow retained activities. Their external expo-sure rates, normalized to administered activ-ity, are considerably lower than thoseencountered in benign thyroid disease

2

patients. Estimates of retained activities ofup to 200 mCi resulted in estimates of effec-tive dose of 0.5 rem to the family members ofthyroid cancer patients treated with 131I.2,3

In May 1997, the NRC amended itsregulations with regards to the release ofpatients administered radioactive material,specifically 10 CFR 35.75.4 This new rulingestablished release criteria based on thepotential effective dose equivalent to individ-uals exposed to the radioactive patient, ratherthan the patientís retained activity or the doserate at one meter. This permitted considera-tion of patient-specific kinetic and dosimet-ric data. The new regulation stipulates thatthe anticipated dose to individuals exposed topatients administered radioactive materialsmust be less than 0.5 rem. This dose-basedlimit better expresses the NRC’s concernswith the health and safety of individuals whomay be exposed to the patient. This isreflected in guidance provided by the NRC’sRegulatory Guide 8.39 entitled “Release ofPatients Administered RadioactiveMaterials.” 5

Regulatory analysis concluded thatthe new dose-based limit is acceptableaccording to current radiation protectionprinciples.6 Anticipated benefits from thechange included an improvement in thepatients’ quality of life, a decrease in thenumber of required hospital admissions andultimately a contribution toward the mini-mization of national health care costs.

NRC REVISED REGULATION10 CFR PART 35.75

The revised 10 CFR Part 35.75applies to patients containing radioactivematerial in the form of permanent implantsand radiopharmaceuticals. This revisionallows the license holder to release a patientfrom its control when the total effective doseequivalent (TEDE) to exposed individuals asa consequence of the release is less than 5mSv (500 mrem).

In implementing this regulatoryrequirement, the NRC regulations stipulatethat three guidelines be observed. First, alicensee may authorize the release from itscontrol any individual who has been admin-istered radiopharmaceuticals or permanentimplants containing radioactive material ifthe TEDE to any person from exposure to thereleased patient is not likely to exceed 5 mSv(500 mrem).

Second, a licensee shall provide thereleased individual with instructions, includ-ing written instructions, on actions recom-mended to maintain doses to exposed indi-viduals as low as reasonably achievable (theALARA concept). These instructions are tobe given to individuals if the TEDE to anyexposed individual has the potential toexceed 1 mSv (100 mrem). If the individualis breast-feeding, and if the dose to her childdue to uninterrupted nursing could exceed1 mSv (100 mrem), then special instructionsmust be issued.

Third, each licensee is required tomaintain a record, for three years after thedate of release, of the basis for authorizingthe release of an individual if the TEDE iscalculated using patient-specific parameterssuch as effective half-life and consideration oftissue shielding. The licensee is also requiredto maintain a record documenting that instruc-tions were provided to a breast-feedingwoman if the radiation dose to the infant orchild from continued breast-feeding could re-sult in a TEDE exceeding 5 mSv (500 mrem).

HOW LICENSEES CAN IMPLEMENTTHE NEW REGULATIONS

According to Regulatory Guide 8.39“Release of Patients Administered Radio-active Material,” patients may be releasedbased on any of the following criteria:• Administered radioactivity,• Retained radioactivity,• Measured dose rate, and• Patient-specific dose calculation.

3

The most straightforward methodemploys the administered or retainedradioactivity as the basis for the release.Assumptions include a point-source patientgeometry, no attenuation by tissue or othershielding, an occupancy factor of 1.0 (at adistance of 1 meter) if the physical half-lifeof the radionuclide is less than one dayand 0.25 if the half-life is greater than oneday, and no biological elimination. Licenseescan use a “default” table provided inRegulatory Guide 8.39, a portion of which isreproduced in Table 1. For example, an

administered 131I radioactivity under 33 mCiis acceptable for the release of patients fromthe licensee’s control. This method may alsobe employed to release patients from hospi-talization when the retained radioactivity hasfallen below the tabulated values, regardlessof the administered activity. Note that novalues are listed in Regulatory Guide 8.39for pure beta emitters such as phosphorus-32,yttrium-90 or strontium-89. This is due tothe very low external radiation hazard posedby patients who have been treated with theseradionuclides.

Patients may also be released basedon the measured dose rate at one meter.Table 1 gives the dose rates below whichpatients may be released from medical isola-tion for selected radionuclides. For example,a patient who has been administered 131I maybe released when the dose rate falls below7.0 mrem per hour.

Licensees may release patients withradioactivity or dose rates greater than thoselisted in Regulatory Guide 8.39 if a case-spe-cific dose calculation is performed. Thistype of calculation permits the use of patient-specific factors such as tissue attenuationand biological clearance. Utilizing data pub-lished in NRC Regulatory Guide 8.39 foruptake fractions and effective half-lives for131I thyroid cancer and hyperthyroidismpatients, calculations demonstrate that up to221 mCi of 131I sodium iodide may be admin-istered for thyroid cancer, and up to 57 mCi

may be administered for hyperthyroidism ifan occupancy factor of 0.25 is assumed. Thismethod can be applied to other labeledagents, as long as specific biological clear-ance data are available. Biological clearancedata obtained from a group of patients maybe applied to individuals, and in thoseinstances for which a case-specific calcula-tion applies to more than one patient release,the calculation need not be performed repeat-edly. For example, by applying the formulaand parameters found in Regulatory Guide8.39, all thyroid cancer patients could bereleased without any calculation if theadministered activity is less than 221 mCi orthe dose rate at one meter was less than 48.5mrem/h (assuming an occupancy factor of0.25). Alternatively, a patient’s specific indi-vidual clearance curve, as measured with atracer dose prior to therapy, may be used tocalculate the limiting dose for that patient.

Table 1. Examples of Radionuclide Activities & Dose Rates for Authorizing Patient Release

Radionuclide Radioactivity at or below which Dose rate @ 1 meter, at or below whichpatients may be released patients may be released

(GBq) (mCi) (mSv/hr) (mrem/hr)131I 1.2 33 0.07 7153Sm 26 700 0.3 3099mTc 28 760 0.58 58198Au 3.5 93 0.21 21

4

Use of this method should always be appliedto research or IND applications for investiga-tional therapeutic radionuclides.

REQUIRED INSTRUCTIONS TOPATIENTS

Written instructions should be specif-ic to the patient’s clinical diagnosis, andshould not compromise the patient’s care orthe judgment of the physician. For 131Ipatients, written instructions are required if apatient-specific dose calculation is per-formed, if the dose rate at 1 meter is greaterthan 2.0 mrem/hr or if the administered activ-ity is greater than 7.0 mCi (see Table 2).Criteria for other radiopharmaceuticals arelisted in Regulatory Guide 8.39. The contentof the written instructions should includeprecautions to reduce the spread of contami-

write the proper ALARA patient guidelinesto be followed, as well as the length of timefor each instruction to be followed.8

Additional instructions must beissued to women who are nursing, if the doseto the infant would exceed 1 mSv (100 mrem)if nursing were continued. The administeredactivities of 131I and other selected radionu-clides that would result in doses to the infantexceeding 1 mSv are listed in Table 3. Theinstructions to nursing mothers shouldinclude guidance on the discontinuation orinterruption of breast-feeding, and the poten-tial adverse effects to the infant if the instruc-tions are not followed. For any given radio-pharmaceutical, these effects include injuryto the blood-forming elements in the bonemarrow, the bone surfaces and any tissues

5

nation, minimizing time spent in publicplaces including sporting events, shoppingcenters, theaters and public transportation,the importance of maintenance of distancefrom others, and the avoidance of sleepingtogether for a specific time period. Thepatient must also be instructed in regards tothe time period during which these instruc-tions should be observed.

The NRC has stated that the instruc-tions provided in a pamphlet published by theSociety of Nuclear Medicine are sufficient infulfilling the requirement for written instruc-tions.7 Revisions in this pamphlet over theyears now require the treating physician to

that might preferentially concentrate theingested radioactivity. It is noteworthy that theradioactivity values listed in Table 3 fall withinthe range of administered activities for diag-nostic studies as well as therapeutic proce-dures. In the specific case of 131I, whichaccounts for the vast majority of radionuclidetherapy procedures, the nursing mother shouldbe advised of the potential for adverse effectsto the infant’s thyroid gland, including hypo-thyroidism or the development of thyroid cancerlater in life. If the dose to the infant were toexceed 5 mSv, then documentation thatinstructions were provided must be maintainedfor at least three years following release.

Table 2. Activities and Dose Rates for Selected Radionuclides That Require Instructions

Radionuclide Radioactivity above which Dose rate @ 1 meter above whichinstructions are required instructions are required

(GBq) (mCi) (mSv/hr) (mrem/hr)131I 0.24 7 0.02 2153Sm 5.2 140 0.06 699mTc 5.6 150 0.12 12198Au 0.69 19 0.04 4

MAINTENANCE OF REQUIREDRECORDS

If the release was based on eitherpatient-specific dose calculation or dose rate,records must be maintained for a minimumof three years. No records are required if therelease is based on the administered (orretained) activity, and the activity is less thanthe levels found in Regulatory Guide 8.39(33 mCi for 131I). Records should include apatient identifier, radionuclide, date and timeof administration, administered radioactivity,date and time of patient release, estimateddose to exposed individuals and the methodemployed to calculate the dose. The descrip-tion of the method should include patient-specific factors such as any changes in occu-pancy factor (the fraction of a day duringwhich an individual is within one meter ofthe patient) or biological clearance parame-ters. Similarly, documentation of requiredinstructions provided to breast-feedingwomen must be maintained for three years(see Table 3).

COMPUTATION OF DOSE TOEXPOSED INDIVIDUALS

A central tenet of the “dose-based”limit is the requirement that the licenseequantitatively estimate the radiation dose to aperson who spends time in proximity to apatient emitting penetrating radiation. Thedose to an exposed individual depends uponmany factors. These include the exposure

rate constant of the radionuclide (the expo-sure rate, in roentgens per hour, measured atone centimeter from a source of one milli-curie activity), the physical half-life of theradionuclide, the biological clearance of theradiopharmaceutical and its metabolic prod-ucts, the distance the person is from thepatient, and the fraction of the total t timespent at that distance (occupancy factor). Intheory, the total dose is the time integral ofthe dose-rate as measured at the spatial posi-tion of the person relative to the patient.Since the spatial position varies unpre-dictably with time, it would seem that theproblem is intractable. In practice, simplify-ing assumptions can be made which makethe computation of the dose to an exposedindividual practical.

The factor “34.6” is a product of theconversion of days to hours (24.0) and thetotal integral of the exponential function(inverse of the natural log of 2.0 =1.44).

For example, suppose a patient con-tains 33 millicuries of 131I, and an exposedindividual stands one meter away from thepatient for six hours per day, seven days perweek for one year. Suppose there is no bio-logical excretion of radioiodine. If the expo-sure constant for 131I is 2.2 R / hr per mCi atone cm, what is the total dose to the exposedindividual over the one-year period? In thiscase, E = 0.25, T = 8.06 days, t = 365 daysand Qo = 33 mCi. Substituting into the aboveformula, we see that the exponential term

6

Table 3. Radiopharmaceutical Activities That Require Instructions and Records WhenAdministered to Patients Who Are Breast-Feeding an Infant or Child

Radiopharmaceutical Radioactivity above which Radioactivity above which ainstructions are required record is required

(MBq) (mCi) (MBq) (mCi)131I Sodium Iodide 0.01 0.0004 0.07 0.0267Ga Citrate 1 0.04 7 0.2201Tl Chloride 40 1 200 599mTc Pertechnetate 100 3 600 15

essentially vanishes, since t >> T, and thatD(t) = 0.5 rem. This is the origin of the33-millicurie “default” value for 131I given inTable 1. Other radionuclides will have dif-ferent exposure rate constants and differentphysical half-lives. This will result in a widerange of values for permissible retainedradioactivity at the time of release; however,all releases would be based on the same max-imum permissible radiation dose (0.5 rem).In practice, a licensee would assume that D(t)is 0.5 rem (or some other lower target value)and solve the above equation for Qo to obtainthe maximum permissible retained activity atrelease.

The above calculation assumes thatthe patient is a point source, that there is nobiological clearance of radioactivity and thatthe patient’s tissue is not attenuating thegamma radiation. Because the patient indeedprovides some self-shielding, and mostradionuclides are subject to biological clear-ance processes, the above computation isquite conservative. In practice, the actualdose will be lower. For this reason, the NRChas enabled licensees to modify the assump-tions underlying the above calculation so thatpatient-specific factors may be taken intoaccount. The patient-specific calculation ofthe dose to exposed individuals may incorpo-rate the use of any of four patient-specific

factors including:1. Retained Radioactivity: May be

instead of administered radioactivity.2. Occupancy or Exposure Factor

(E): Assumes individuals will spend variabledistance and time in the proximity of thepatient. A value of 0.25 may be used withoutjustification. A patient who lives alone andis generally isolated from other people wouldenable a value of 0.125 to be used with justi-fication. A patient requiring extensive carewhile at home would require a higher valueof the occupancy factor (perhaps 0.50 - 0.75)to account for the increased exposure of theindividual providing care.

3. Effect ive Half-Life (T EFF):Licensees can use a measured TEFF instead ofthe physical half-life (Tp) of administeredradionuclide.

4. Attenuation or Shielding byTissue: Licensees can use a measured doserate, since this measurement includes attenu-ation by the patient’s tissues. In this case, thedose rate, in rem per hour as determined byusing a calibrated ion chamber at one meterfrom the patient, would replace the termΓQo / r 2 in the above equation.

The dose limit of 0.5 rem, as set forthin the regulatory criteria, is expressedas TEDE. The TEDE is not a directly meas-urable physical quantity. It is a weighted

7

The following formula may be used to calculate potential exposure to exposedindividuals, if biological clearance is not taken into account:

D (t) = 34.6 Γ Q0TE (1-e-0.693 t / T )

r2

Where D (t) = Accumulated dose to time t, in remsT = Physical half-life in daysE = Occupancy factor that accounts for different occupancy times and distances

when individual is near patient. For example, if the individual spends 6 hoursper day at 1 meter from the patient, then E = 6 / 24, or 0.25

Γ = Exposure rate constant for a point source, R / hr per mCi x hr at 1 cmQ0 = Initial activity at the start of time intervalt = Exposure time in daysr = Distance in centimeters, 100 cm (1 meter) is usually used

average of the radiation-absorbed doses to anumber of tissues that are considered to besignificant with regard to genetic effects andthe induction of cancer. In order to correctlycalculate TEDE, one must know the radiationdoses due to (1) external gamma radiationemitted by the released patient and (2) inter-nally deposited radionuclides that are a con-sequence of ingestion of contaminationderived from the urine, saliva and perspirationof the released patient. A rigorous computa-tion of TEDE is very difficult, and requiresmathematical techniques not readily availableto most licensees. However, the NRC permitslicensees to use simplifying assumptionswhen computing the TEDE. First, the contri-bution to TEDE from external radiation maybe derived from a single measurement of thedose rate, taking into account the physical oreffective half-life, using a suitably calibratedion chamber at a point one meter from thepatient. This will result in an overestimationof the external component, since the targetindividual’s muscle and adipose tissue willreduce the radiation dose to bone marrow,lung, gonads and other biologically signifi-cant tissues through attenuation. Althoughnot strictly correct, this “point measurement”approximation of the TEDE will result in aconservative estimate of the dose to exposedindividuals. Second, the contribution toTEDE due to the internalization of contami-nation may be neglected if its estimated con-tribution to the total dose is less than 10% of

the external dose estimate, according toRegulatory Guide 8.39. This is based onobservations of low thyroid uptake of 131I infamily members of patients treated for hyper-thyroidism or thyroid cancer with radioiodineand released. Therefore, licensees can usuallyuse the measured dose rate at 1 meter fromthe patient, in conjunction with the physicalor effective half-life, as the sole basis for thecomputation of TEDE.

Appendix B of Regulatory Guide 8.39demonstrates how licensees may calculatethe external radiation dose to exposedindividuals from patients who have beentreated with 131I sodium iodide for hyperthy-roidism and metastatic thyroid carcinoma. Athree-component model (Equation B-5,Appendix B), which accounts for radioactivi-ty retained during an initial non-void period,clearance via urinary and gastrointestinalroutes and retention by intact thyroid gland orthyroid remnants, is used to estimate the totaldose to an exposed individual from the timeof administration to total decay. The parame-ters of the model include the effective half-time and fractional uptake of each compo-nent, which are tabulated in Table B-1 ofAppendix B. Using the maximum permissi-ble dose of 0.5 rem, Equation B-5 may besolved for the maximum permissible adminis-tered activity or maximum permis-sible expo-sure rate at one meter. Table 4 below showsthe results of such calculations assumingthree different occupancy factors.

8

Table 4. Computation of Maximum Administered 131I Activity and Initial Dose Rate at1 Meter for Different Occupancy Factors

Thyroid Carcinoma Hyperthyroidism

Occupancy Maximum Dose rate at 1 Maximum Dose rate at 1factor activity at meter (mrem/hr) activity at meter (mrem/hr)

release (mCi) release (mCi)

0.125 304 66.8 101.4 22.3

0.25 221 48.6 57 12.4

0.50 143 31.4 30.0 6.6

PRACTICAL APPLICATION OF THECRITERIA

Application of these new criteria mayseem complicated, especially with regard tothe provision of “customized” instructions toindividual patients. However, it is possible touse look-up tables, spreadsheets, databasesor Internet-based applications to streamlinethe procedure.9,10 In addition, Zanzonico andco-workers have done extensive work todevelop a generalized algorithm for deter-mining the time of release and the duration ofprecautions for radionuclide therapy patientsand their families.11 Application of such algo-rithms will provide an improved basis forrelease times and consistency to the post-release instructions.

A straightforward procedure using aquestionnaire and a template set of instruc-tions is presented below. This procedurereflects the practice of one of the authors(SGM) and colleagues at the Ohio StateUniversity Medical Center.

1. Patient identified by his/her physi-cian as a candidate for radionuclide therapy.

2. Physician indicates the radionu-clide and radioactivity to be administered.

3. Prior to scheduling the radionu-clide therapy, patient is asked to complete atwo page questionnaire (see Figure 1) whichsolicits information regarding the individ-ual’s general health, family members present-ly at home, sleeping arrangements, pregnan-cy status for any individuals sharing thehome, type of work performed, medical con-ditions which may require extensive medicalcare and travel arrangements for returninghome.

4. Medical physicist reviews ques-tionnaire and determines if patient is candi-date for treatment as an outpatient. If patientis eligible for release as outlined in 10 CFRPart 35.75, a dose estimate is performed toensure no individual receives a dose greaterthan 0.5 rem from exposure to the patient.

5. Prior to the administration of the

radiopharmaceutical, the patient is asked toreview written instructions (see Figure 2) forthe purpose of ensuring the radiation dose toexposed individuals is less than 0.5 rem.

6. Patient is asked to sign the writteninstructions and a copy provided.

7. After the patient receives theradiopharmaceutical, the patient is surveyedwith an ion chamber and the results recordedon a patient release form.

Figure 1 is an example of the type ofquestionnaire that would be filled out bythe authorized nuclear medicine physician,the radiation safety officer or other appropri-ately designated personnel while interview-ing the patient. The questionnaire depictedin Figure 1 is used by one of the authors(SGM) at the Ohio State University MedicalCenter. The information collected is usefulin assisting the physician and radiationsafety officer in making a general assessmentof the patient’s suitability for release, select-ing the appropriate occupancy factors for usein estimating the dose to exposed individuals,and in providing additional guidance tothe patient when reviewing the writteninstructions.

The sample post-discharge instruc-tions shown in Figure 2 are also used at theOhio State University Medical Center. Theyprovide the patients with ways in which theycan modify their normal interactions withfriends, colleagues and family members sothat the radiation exposure to others is mini-mized. This set of instructions is specific to131I, which is the radionuclide used in virtual-ly all the therapeutic procedures performedin the United States for which writteninstructions are required. This institution-specific set of instructions is similar to thatfound in the pamphlet published by theSociety of Nuclear Medicine7 mentioned ear-lier. The medical physicist as identified inthe “Special Instructions” section would pro-vide the lengths of time that the patientshould avoid certain interactions with others.

9

10

11

12

13

*Patient-specific; required only for anti-lymphoma antibody treatments.

**Patient-specific; required only for hyperthyroidism treatments.

Household Information

Type of Dwelling: !Single-Family "Multi-Family "Apartment "Dormitory

Is anyone in the household: Pregnant # Breastfeeding #

Enter Data on Household Members:

An alternative approach to generatingthe required instructions and documentationinvolves the use of an on-line form accessedvia the Internet. Radiation safety personnelcan enter the required patient-specificinformation, dates, exposure rates andeffective half-lives via radio buttons, textboxes and check boxes. This information iselectronically submitted to a Web server,which computes the expected radiation doseto exposed individuals and the lengthsof time the patient should observe certain

precautions. These values are used toproduce a suitable ìpost-discharge instruc-tionsî document that can be printed from theWeb browser. Similarly, the program cangenerate the required documentation of theexpected dose and the method of calculation.This approach is used by one of the authors(RER) at Duke University Medical Center.A portion of Duke’s on-line form, whichincludes textboxes, radio buttons and check-boxes used for data entry, is depicted inFigure 3.

14

Figure 3. A Portion of Duke University’s Online Form

Activity Activity at Time of Release Exp. Rate *Effective half-life **Thyroid UptakeAdministered (mCi): Release (mCi): (mR/hr): (days): Value (%):

PATIENT: Household Member 2: Household Member 3: Household Member 4:"Male !Female "Male !Female "Male !Female "Male !Female

Age Age Age Age

Household Member 5: Household Member 6: Household Member 7: Household Member 8:"Male !Female "Male !Female "Male !Female "Male !Female

Age Age Age Age

Transportation/Visitors/Work/School Information

Transportation Home: Visitors (check all that apply):

"Private Car, Alone Regular # Children # Pregnant #!Private Car, Shared (less than 50 miles) Breast-feeding #"Private Car, Shared (50-200 miles)"Private Car, Shared (over 200 miles)"Public Conveyance (airplane, bus, train)

15

The estimated dose to exposed individuals for this patient due to external gammaradiation is given by:

DE = 34.6 x (10.0 mrem/hr) x [0.97 x (3.0 d x 0.25) + 0.03 x (8.04 d) x 0.75]DE = 314 mrem

EXAMPLESTo illustrate the principles outlined

above, we present three examples of howthey may be implemented to release patientsand provide them with appropriate home-going instructions.

(1) A 47-year-old man is treated forlymphoma with a monoclonal antibodylabeled with 131I. He lives with his wife anda 19-year-old daughter. Despite his illness,

greater than the default 7.0 mrem per hour(see Table 1), then the release must be docu-mented, and the documentation maintainedfor at least three years. Because the dose rateexceeds 2 mrem per hour (see Table 2), thepatient must be supplied with written post-discharge instructions (see Figure 2), a copyof which must be maintained for three yearsalong with the dosimetry documentation.

he is active and continues to work as a parkranger. Measurement of the clearance ofantibody with a small test dose demonstrateda single-exponential clearance with an effec-tive half-life of 3.0 days in this patient.Immediately after administration of the ther-apy dose, the medical physicist measures thedose rate at a distance of 1 meter from thepatient and determines it to be 10.0 mrem perhour. What will be the expected TEDE forindividuals exposed to this patient? Is he acandidate for immediate release?

This patient is capable of self-careand has simple home and employment situa-tions. Therefore, the default occupancy fac-tor of 0.25 may be used for the single-expo-nential component in the dose calculation. Inaddition, it is assumed that the patient doesnot void for the first eight hours followingadministration. This requires inclusion of asecond component in which the only clear-ance is by physical decay. For this compo-nent, an occupancy factor of 0.75 is recom-mended. (see Regulatory Guide 8.39).

Because the calculated TEDE is lessthan 0.5 rem, this patient is a candidate forimmediate release. Since the release is basedon an effective half-life rather than thedefault physical half-life, and a dose rate

(2) A 28-year-old woman is beingevaluated for a possible recurrence ofHodgkin lymphoma. She is given 4.0 milli-curies of 67Ga-gallium citrate intravenouslyand told to return in 48 hours for an imagingprocedure. Following administration of theradiopharmaceutical, she tells the technolo-gist how much she enjoys nursing her3-month-old infant. What instructionsshould she be given?

In general, it should be determined ifthe patient is nursing or pregnant beforeadministering radioactive material, to permitan informed decision as to whether or not todefer the procedure. In this case, the admin-istered activity of 67Ga is well above the levelfor which instructions to nursing mothersmust be supplied (0.2 millicuries; see Table3). Nursing should be interrupted until theretained activity is less than 0.04 mCi(Regulatory Guide 8.39,Table 3, Column 1).This patient should be instructed to discon-tinue breast-feeding her child for at least onemonth, and documentation of this eventshould be maintained for at least three years.

(3) A 75-year-old male patient isbeing considered for treatment for thyroidcancer with 200 millicuries of 131I sodiumiodide following total thyroidectomy. He is

incontinent of urine and requires extensivehome nursing care from his daughter. Twochildren, aged 10 and 12, also live with him.Is this patient a candidate for immediaterelease? If not, when could he be released?

In this case, an occupancy factor of0.25 at 1 meter would not be appropriate,given the requirement for extensive nursingcare. A value of 0.50 is chosen instead.According to Table 4, the maximum adminis-tered activity for an occupancy factor of 0.50is 143 millicuries. This patient would not bea candidate for immediate release if a treat-ment activity of 200 millicuries were used.In addition, this patient’s incontinence sug-gests that the potential for ingestion of con-tamination may present a significant risk tothe daughter and small children in the house-hold. To be conservative, the treating physi-cian and radiation safety officer decide thatrelease at the default dose rate for whichinstructions are required, but not documenta-tion (2.0 mrem per hour for 131I), is appropriate.In this case written post-discharge instruc-tions should include additional precautions,such as wearing protective gloves when han-dling disposable diapers or linens.

DISCUSSIONThe revised dose-based release criteria

have several advantages over the olderactivity- and dose-rate-based criteria. Mostimportantly, required hospital stays arereduced, which will help minimize healthcare costs and may also provide emotionalbenefits to patients and their families.6 Theradiation exposure to the occupationallyexposed health care workers who care forthese patients will be reduced. The primarydisadvantage of releasing patients (who havereceived radioactive material) into the unre-stricted environment is the higher exposureto radiation to other individuals than thoseincurred if the patient remained isolated in aninstitution. However, with proper instruc-tion, the doses to those people who live with

the patient should remain low. Indeed,Grigsby and colleagues at the WashingtonUniversity School of Medicine recently fol-lowed 65 family members of 30 outpatientswho were treated with 131I sodium iodide forthyroid cancer. Despite administered activi-ties between 76 mCi and 151 mCi, the aver-age measured dose to family members wasonly 0.24 mSv (24 mrem), with a maximumof 1.09 mSv (109 mrem).12

A dose-based release criterion has anadvantage over the activity-based criteria inthat it standardizes the conditions for releaseamong the growing number of radionuclidesbeing used in nuclear medicine practice, par-ticularly for therapy. Patients can now bereleased from licensee control regardless ofthe quantity of radioactivity they receive aslong as the total dose to an individual is lessthan 500 mrem. These revised regulationsmake it possible to perform some radionu-clide therapy procedures on an outpatientbasis. This should improve the utilization ofnewer forms of therapy for bone pain pallia-tion and treatment of solid and hematologiccancers.13

Authorized users of radioactive mate-rials in the eighteen states under the jurisdic-tion of the Nuclear Regulatory Commissionmust follow the new regulations. Users in the32 Agreement States should verify that theirstate authorities have amended their regulationsto incorporate these changes, and amendtheir institutional license conditions if required.

As discussed above, the methods ofcalculating the potential dose to individualsexposed to the patient permitted by the newregulations can be expected to result in anoverestimation of absorbed dose due to sim-plifying assumptions. Sparks and col-leagues, using powerful Monte-Carlo dosecalculation methods, have demonstrated thatthe use of a single measurement of dose-rateat 1 meter from the patient overestimates theTEDE by about 60%.14 It is possible thatimprovements to the computation of TEDE

16

can be made to address the issues (includingattenuation and variable organ geometry)which lead to overly conservative estimatesfor the potential radiation dose. Even with-

out such refinements, straightforward appli-cations of the new release criteria provide amuch-improved method for patient care,while assuring the safety of the public.

17

REFERENCES

1. National Council on Radiation Protection(NCRP). Limitation of Exposure toIonizing Radiation. NCRP Report No.116. Bethesda: National Council onRadiation Protection (NCRP), 1993.

2. Zanzonico PB. Radiation dose to patientsand relatives incident to 131I therapy.Thyroid. 1997;7(2):199-204.

3. Zanzonico PB, Becker DV, Goldsmith SJ.Release criteria for patients receivingtherapeutic amounts of radioactivity:A re-evaluation based on publishedd o s i m e t r y d a t a . J N u c l M e d .1997;38(5):229P.

4. U.S. Nuclear Regulatory Commission.Criteria for the Release of IndividualsAdministered Radioactive Material.10 CFR Parts 20 and 35: 62 FR 4120;1997.

5. U.S. Nuclear Regulatory Commission.Release of Patients Administered Radio-active Materials. Regulatory Guide 8.39.Washington, DC: USNRC, 1997.

6. Schneider S, McGuire SA. RegulatoryAnalysis on Criteria for the Releaseof Patients Administered RadioactiveMaterial. NUREG-1492 (Final Report).Washington: USNRC, 1996.

7. Society of Nuclear Medicine. Guidelinesfor Patients Receiving RadioiodineTreatment. Reston: Society of NuclearMedicine, Inc., 1997.

8. Hung JC. Written instructions for therelease of patients administered radio-pharmaceuticals. J Nucl Med. 1997;38(11):1831.

9. Cormack, J, Shearer J. Calculation ofradiation exposures from patients to whomradioactive materials have been adminis-tered. Phys Med Biol. 1998;43(3):501-516.

10. Reiman R, Yoshizumi T. Radiation safe-ty program documentation by database.Med Phys. 1999;26(6):1123.

11. Zanzonico PB, Siegel JA, St. Germain J.A generalized algorithm for determiningthe time of release and the duration ofpost-release radiation precautions follow-ing radionuclide therapy. Health Phys.2000; 78(6):648-659.

12. Grigsby PW, Siegel BA, Baker S,Eichling JO. Radiation exposure fromoutpatient radioactive iodine (131I) therapyfor thyroid carcinoma. JAMA.2000;283(17):2272-2274.

13. Siegel JA. Revised nuclear regulatorycommission regulations for release ofpatients administered radioactive materi-als: outpatient iodine-131 anti-B1 therapy.J Nucl Med. 1998;39(suppl):28S-33S.

14. Sparks RB, Siegel JA, Wahl RL. Theneed for better methods to determinerelease criteria for patients administeredradioactive material. Health Phys.1998;75(4):385-388.

18

QUESTIONS

1. Which of the following radionuclidesdoes NOT present a significant EXTER-NAL radiation hazard to members of thepublic?

a. Iodine-131 b. Iridium-192c. Iodine-125d. Strontium-89

2. Under the patient release criteria adoptedby the NRC in 1997, what is the maxi-mum exposure an individual may receivefrom patients who have been adminis-tered radioactive material?

a. 5000 mremb. 5 remc. 500 mremd. 100 mrem

3. Based on the release criteria employedPRIOR TO 1997, the licensee couldrelease a patient containing radioactivematerial under which of the followingbody burden / dose rate conditions?

a. 300 mCi or 50 mrem/hour @ 1 meterb. 3 mCi or 500 mrem/hr @ 1 meterc. 30 mCi or 5 mrem/hr @ 1 meterd. 0.3 mCi or 0.5 mrem/hr @ 1 meter

4. In what section of the Code of FederalRegulations (CFR) is the “Release ofPatients Administered RadioactiveMaterial” addressed?

a. 10 CFR 20.1902b. 10 CFR 35.75c. 10 CFR2d. 10 CFR 35.900

5. Which of the following phrases does theacronym “ALARA” represent?

a. As Long As Required byAdministrators

b. As Limits And Records Agreec. As Low As Reasonably Achievabled. As Long As the Regulators aren’t

Aware

6. Written instructions must be given toindividuals whenever the dose (TEDE) toexposed individuals may exceed ______.

a. 10000 mremb. 1 remc. 10 remd. 100 mrem

7. Above what dose (TEDE) to an infantor child as a result of breast-feedingshould instructions be given to thenursing mother?

a. 5000 mremb. 50 remc. 100 mremd. 10 mrem

8. Which of the following is currently NOTa criteria for the release of patientsadministered radioactive material?

a. release based on administeredactivity

b. release based on a patient specificdose calculation

c. release based on retained activityd. release based on the total counts

obtained from whole body imaging

19

9. Which of the following doses (TEDE) tothe infant or child as a result of continuedbreast-feeding requires the licensee tomaintain records?

a. 500 mremb. 5 remc. 100 mremd. 5000 mrem

10. How long must the licensee maintainrecords which authorizes the release ofan individual after the date of releasebased on the calculated TEDE?

a. 10 yearsb. 1 yearc. 3 yearsd. 3 months

11. Which of the following methods below isNOT acceptable for calculating theTEDE?

a. Considering shielding by tissueb. Using the effective or biological

half-lifec. Using an occupancy factor of less

than 0.25 @ 1 meter withoutjustification

d. Using an occupancy factor of greaterthan 0.25 @ 1 meter

12. Adoption of the new dose-based releasecriteria were based on all the followingEXCEPT:

a. Comments from interested partiesb. Accepted principles of radiation

protectionc. Vote by a subcommittee of the

Senated. Recommendations of the Advisory

Council on the Medical Uses ofIsotopes

13. All of the following are DISADVAN-TAGES of the old activity-based releasecriteria EXCEPT:

a. Were appropriate for 131I onlyb. Required hospitalization for almost

all thyroid cancer patientsc. Added to the cost of medical cared. Did not consider stochastic

radiogenic risks

14. Which of the following is NOT an advan-tage of the new dose-based release criteria?

a. Fewer patients require hospitalizationb. Patients can be released from

hospitalization earlierc. NRC has provided dose and activity

tables for common radionuclidesd. No documentation is required

15. The contents of written instructions topatients should include:

a. Measures to reduce the spread ofcontamination

b. Minimizing time spent in publicplaces

c. The length of time the patient shouldfollow the precautions

d. All of the above

16. Which of the following is the primaryreason for giving written instructions topatients who have been released in accor-dance to 10 CFR Part 35.75?

a. Avoiding legal liability by the licenseeb. Providing the patient with methods

to reduce exposures to members ofthe general public

c. Providing the patient with instructionswhich would increase exposuresabove the 500 mrem TEDE

d. Helping to increase the effect of thetherapeutic radionuclide

20

17. Which of the following criteria may NOTbe used for the release of patients admin-istered radioactive material?

a. Release based on an administeredactivity

b. Release based on a measured doserate

c. Release based on an estimated doseto individuals exposed to the patient

d. Release based on expiration of thepatient’s health insurance

18. Model post-release instructions forpatients may be found in a pamphletpublished by the:

a. Justice Departmentb. Bureau of Alcohol, Tobacco and

Radioactive Materialsc. Society of Nuclear Medicined. Nuclear Regulatory Commission

19. According to Regulatory Guide 8.39, themaximum administered (or retained)radioactivity for which a licensee couldpermit the release of a patient receivingiodine-131, without a dose-rate measure-ment or patient-specific calculation, is:

a. 66 mCib. 133 mCic. 7 mCid. 33 mCi

20. According to Regulatory Guide 8.39, themaximum dose rate at 1 meter for whicha licensee could permit the release of apatient receiving iodine-131, without apatient-specific calculation, is:

a. 7.0 mrem/hrb. 10.0 mrem/hrc. 7.0 mrem/mind. 1.0 rem/hr

21. How long are records required to be keptafter the date of release for patientsreleased based on a measured dose rate ora patient-specific dose calculation?

a. 5 yearsb. 3 monthsc. 6 monthsd. 3 years

22. For what minimum period of time arerecords documenting that instructionswere provided to breast-feeding patientsrequired to be kept after the date ofrelease if a child or infant were to receivea TEDE of 500 mrem from the continua-tion of breast-feeding?

a. 3 yearsb. 3 monthsc. 3 daysd. 3 weeks

23. What piece of information is NOTrequired to be recorded if the patient isreleased based on a patient-specificcalculation of the anticipated dose to anexposed individual?

a. Patient’s ethnic backgroundb. Patient identifierc. Estimated dose to exposed individualsd. Radioactive material, activity, date,

and time of administration

21

24. Which of the following calculationmethods may be employed, if the patientis released on a patient-specific dosecalculation?

a. Occupancy factor at 1 meter is 1.0,if the physical half-life is less thanone day

b. Consideration of shielding bydrywall in the patient’s dwelling

c. Occupancy factor at 1 meter is 0.10,if the physical half-life is greaterthan one day

d. Occupancy factor at 1 meter is 0.10,if the physical half-life is greaterthan eight days

25. The new dose-based criteria reflect theNRC’s concern for:

a. The health and safety of physiciansadministering radioactive materials

b. The health and safety of the publicc. The rising cost of radiopharmaceuticalsd. The rising cost of regulatory

administration

22