Society of Nuclear Medicine Procedure Guideline for the Use ...

Society of Nuclear Medicine Procedure Guideline forthe Use of Radiopharmaceuticalsversion 3.0, approved June 23, 2001Authors: Ronald J. Callahan, PhD (Massachusetts General Hospital, Boston, MA); Henry M. Chilton, PharmD (BowmanGray School of Medicine, Winston-Salem, NC); David A. Goodwin, MD (VA Medical Center, Palo Alto, CA); Donald J.Hnatowich, PhD (University of Massachusetts Medical Center, Worcester, MA); James A. Ponto, MS (University of IowaHospitals and Clinics, Iowa City, IA); Dennis P. Swanson, RPh, MS (University of Pittsburgh, Pittsburgh, PA); and HenryD. Royal, MD) (Mallinckrodt Institute of Radiology, St. Louis, MO).I.Purposedure by affecting the distribution and pharma-cokinetics of the administered agents throughThis guideline was developed by the Society ofan alteration in organ physiology.Nuclear Medicine to describe important factorscommon to most nuclear medicine procedures. Itis intended to guide nuclear medicine practition-III. Common Indicationsers in establishing policies and procedures for theAny procedure which uses a radiopharmaceuticaluse of radiopharmaceuticals in clinical practice.(see specific procedure guideline).This guideline is intended to be concordant withthe regulations of the Nuclear Regulatory Com-mission (NRC) and other state and federal gov-IV. Proceduresernment agencies.A. Clinical Use of Radiopharmaceuticals1. A physician-derived order (e.g., prescription,II. Background Information and Definitionsrequisition) is required for the conduct of allA. Radiopharmaceuticals (also known as radioac-procedures. The order should specify the pro-tive drugs) are drugs that contain radionu-cedure desired, the drug(s) to be used, theclides that emit radiation(s). The distribution ofamount(s) to be administered, the route of ad-the radiopharmaceutical within the body is de-ministration, and, if applicable, the rate of in-termined by the physiochemical properties offusion. Alternately, the order may specify athe drug, the stability of the radiolabel, the pu-standard procedure with the other requiredrity of the radiopharmaceutical preparation,information, i.e., standing orders, specified inthe pathophysiological state of the patient anda routinely updated and physician-approvedthe presence or absence of interfering drugs.procedure manual located within the nuclearDynamic and static images of the distributionmedicine laboratory.of the radiopharmaceutical within the body can2. The prescribing physician is ultimately re-be obtained using a gamma camera, or othersponsible for the safety, quality, and correct-suitable instrument appropriate for the radio-ness of all radiopharmaceuticals preparedpharmaceutical being imaged, e.g., positronand dispensed for administration under hisemitting radiopharmaceuticals. Measurement(her) direction.of radioactivity in specified sites of accumula-3. The nuclear pharmacist is ultimately respon-tion or in biological samples following admin-sible for the safety, quality and correctness ofistration of the radiopharmaceutical can be per-radiopharmaceuticals prepared and dis-formed for non-imaging procedures. Highpensed under his (her) supervision.dose, nonpenetrating radiation in localized4 . The preparation, quality control, dispensingsites of accumulation of the radiopharmaceuti-and patient administration of radiopharma-cal can be useful for therapeutic procedures.ceuticals and adjunctive drugs may be dele-B. Physiologic and pharmacologic interventionsgated to qualified personnel, in accordanceare procedures, which increase the sensitivitywith applicable state and local laws.and/or specificity of a nuclear medicine proce-5. There must be a signed and dated written di-82 • USE OF RADIOPHARMACEUTICALSrective for each patient for I-125 or 1-131nuclear pharmacist; in such instances, thesodium iodide in quantities ≥ l.1 MBq (30 µCi)physician or pharmacist responsible forand for all therapeutic radiopharmaceuticals,preparing the radiopharmaceutical is respon-such as strontium-89.sible for assuring that it meets applicable USP6. The identity of the radiopharmaceutical, pa-specifications.tient and route of administration shall be ver-3. Aseptic procedures must be followed when-ified prior to administration. Female patientsever handling parenteral or ophthalmic ra-who are post-menarche and pre-menopausediopharmaceutical preparations or theirshould be asked about pregnancy, lactationc o m p o n e n t s .and breast-feeding prior to administration.4. A comprehensive radiopharmaceutical qual-Pregnancy testing in females of childbearingity control program should be developed andcapability should be performed prior to ad-implemented. The scope of the programministration of any radiopharmaceutical thatshould be compatible with the type of practicecould potentially result in a dose to an em-and the availability of equipment and person-bryo or fetus of 50 mSv (5 rems) or more (e.g.,nel. The parameters to monitor in a radio-I-131 therapy).pharmaceutical quality control program in-7. The quantity of each radiopharmaceuticalclude: (a) chemical purity; (b) radiochemicaldosage must be determined prior to patientpurity; (c) radionuclide purity; (d) biologicaladministration and must be consistent withpurity (sterility and apyrogenicity); and (e)that ordered by the physician or addressed inpharmaceutical purity (e.g., pH, particle size,the procedure manual of the nuclear medicineabsence of foreign particulate matter).laboratory. The quantity of radioactivity dis-C. Positron Emitting Radiopharmaceuticalspensed should be within 10% of the pre-Radiopharmaceuticals used in positron emissionscribed dose or dosage range and the actualtomography require specialized personnel; facil-quantity administered must be recorded inities and equipment due primarily to the rela-the patient’s medical record.tively short physical half-lives of the radionu-8. Radiopharmaceuticals should not be used be-clides used (2 min to 1.8 hr), their energeticyond the manufacturer’s recommended expi-photon emissions and the chemical synthesesration date/time unless specific quality con-necessary for their preparation. Preparation oftrol testing demonstrates that the product stillPET radiopharmaceuticals must comply withmeets applicable USP specifications at theUSP compounding standards or FDA manufac-time of use.turing requirements. Nuclear medicine practi-9. Any discrepancies shall be resolved prior totioners involved in positron emission tomogra-administration.phy should consult with qualified chemists,B. Elution of Generators and On-Site Preparationpharmacists, physicists and technologists in es-of Kitstablishing and operating a PET program.1. Each time a generator is to be eluted, the gen-D. Record Keepingerator to be eluted and the volume of eluent to1. Records of receipt, usage, administration andbe used should be selected based on the cali-disposal of all radiopharmaceuticals shall bebration and elution history of the generator.kept in compliance with license conditionsThe quantity of radioactivity eluted and theand applicable medical records and radiationconcentration of parent nuclide breakthroughcontrol regulations.must be measured and recorded for each elu-2. Records concerning the receipt of packagestion performed. The extent of breakthroughcontaining radioactive material should in-must be verified to be below the appropriateclude proper identification of contents, in-regulatory limit. The final volume of the elu-spection for physical damage and testing forate, the identity of the person performing theexternal contamination, as required by the ap-elution and the date and time of elution shallpropriate regulatory agency. Appropriatebe recorded. Proper radiation safety proce-records of the receipt of radioactive materialdures must be employed throughout the elu-shall be maintained and stored in accordancetion process. with applicable local state and federal regula-2. Radiopharmaceuticals should be prepared ac-tions. Such records shall address the identitycording to manufacturer’s instructions. Devi-of the radiopharmaceutical, its source, theations from the package insert instructionsamount of activity received and the results ofmay be made by the prescribing physician orradiation surveys and contamination testing.SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL JUNE 2002• 83Any discrepancies must be reported to theministration to the wrong patient. The handlingmanufacturer and/or proper regulatoryand administration of blood products must beagency.subject to special safeguards and procedures, the3. For all radiopharmaceuticals prepared on-goal of which is to eliminate any possibility ofsite, records should include the date and timeadministration to the wrong patient, contamina-of preparation, quantity, volume and concen-tion of the blood by environmental substances,tration of radioactivity used, reagent lot num-and contamination of workers during radiolabel-bers, quality control data, expiration time,ing procedures. waste disposal information, and name or ini-H. Drug Interactions and Altered Distributiontials of the individual responsible for theP a t t e r n spreparation.1. The in vivo distribution of radiopharmaceuti-4. For all radiopharmaceuticals, the identity ofcals can be altered by the radiopharmaceutical, the amount of ra-Concurrent medications and prior diag-dioactivity administered, patient identity,nostic tests (including contrast dye and previ-identity of individual performing the admin-ous radiopharmaceuticals). The nuclearistration, route of administration, and datemedicine practitioner should be familiar withand time of use must be recorded.documented drug interactions and consider5. Appropriate records of radionuclide dose cali-this information when planning the nuclearbrator testing for constancy, accuracy, linearitymedicine procedure to be performed andand geometric variation shall be maintained.when altered distribution patterns are identi-6. Disposal of all radioactive material must befied on patient studies.accomplished in accordance with institu-2. Problems in the formulation of radiopharma-tional, state and federal regulations. Policyceuticals can result in altered distribution pat-and procedures should be developed to as-terns. Appropriate quality control programssure that radioactive material does not entershould identify such problems prior to patientthe normal waste stream of the institution ex-administration. The possibility of a formula-cept in exempt quantities or in exempt formstion-related cause of an altered distribution(e.g., patient excreta).pattern should be considered in evaluation ofE. Adverse Reactions/Product Problemsany unexplained image findings.Adverse reactions associated with administra-tion of radiopharmaceuticals should be investi-V. Issues Requiring Further Clarificationgated and documented. Reports of serious ad-verse reactions and product problems should beNonemade to the manufacturer and to MedWatch.F. Misadministration of RadiopharmaceuticalsVI. Concise BibliographyPolicies and procedures should be developedwhich assure that the correct patient receives theChilton HM, Witcofski RL. Nuclear Pharmacy. An Intro-correct drug, at the correct time, at the correctduction to the Clinical Applications of Radiopharmaceu-dose and by the correct route of administration.ticals. Philadelphia, PA; Lea and Fiebiger: 1986.Misadministrations, also known as medicalHenkin RE, Boles MA, Dillehay GL, et al. The Scientificevents, have been defined by federal and stateBasis of Nuclear Medicine; Part IIB: Radiopharmacy.regulatory agencies and include a timely report-In: Nuclear Medicine. Mosby; New York, NY. 1996.ing requirement. When required, such eventsHladik WB, Ponto JA, Lentle BC, et al. Iatrogenic Alter-should be reported to the appropriate agencyations In Biodistribution of Radiotracers As A Re-within the time frame specified.sult of Drug Therapy: Reported Instances. In:G Special Considerations for Labeled Blood Hladik WB, Saha GB, Study KT (eds): Essentials ofP r o d u c t sNuclear Medicine Science. Baltimore, MD; WilliamsWhile the misadministration of any radiophar-and Wilkins: 1987.maceutical is serious, special precautions mustHung JC, Ponto JA, Hammes RI. Radiopharmaceutical-be implemented to prevent the misadministra-related Pitfalls and Artifacts. Semin Nucl Med l996;tion of radiopharmaceuticals containing blood26:208–255.products, i.e., Tc-99m red blood cells and In-111Kowalsky RJ, Perry JR. Radiopharmaceuticals in Nu-and Tc-99m leukocytes. Procedures which in-clear Medicine Practice. Norwalk, CT: Appleton &volve the removal of blood for radiolabeling andLange: 1987.subsequent reinjection have potential for misad-Laven DL, Shaw SM. Detection of Drug Interactions In-84 • USE OF RADIOPHARMACEUTICALSvolving Radiopharmaceuticals: A Professional Re-proved guidelines to promote the cost-effective use ofsponsibility of the Clinical Pharmacist. J Pharmhigh quality nuclear medicine procedures. ThesePractice l989; 2:287–298.generic recommendations cannot be applied to all pa-Nuclear Pharmacy Practice Guidelines. Washington,tients in all practice settings. The guidelines shouldDC; American Pharmaceutical Association: 1995.not be deemed inclusive of all proper procedures orRadiopharmaceuticals for Positron Emission Tomogra-exclusive of other procedures reasonably directed tophy-Compounding. In: USP 24 and NF 19.obtaining the same results. The spectrum of patientsRockville, MD: The United States Pharmacopeialseen in a specialized practice setting may be quite dif-Convention, Inc: 1999:1988–1990.ferent than the spectrum of patients seen in a moreSaha GB. Fundamentals of Nuclear Pharmacy, Fourthgeneral practice setting. The appropriateness of aEdition. New York, NY; Springer-Verlag:1992.procedure will depend in part on the prevalence ofSampson CB. Textbook of Radiopharmacy: Theory anddisease in the patient population. In addition, the re-Practice, Third Edition. Amsterdam; Gordon andsources available to care for patients may vary greatlyBreach Science Publishers. 1999.from one medical facility to another. For these rea-sons, guidelines cannot be rigidly applied.Advances in medicine occur at a rapid rate. TheVIII.Disclaimerdate of a guideline should always be considered inThe Society of Nuclear Medicine has written and ap-determining its current applicability.