I. Purpose
This Standard Operating Procedure is intended to guide nuclear medicine practitioners in the use of radiopharmaceuticals in research practice. This SOP is intended to be concordant with UAMS policies and regulations, the regulations of the Nuclear Regulatory Commission (NRC), and the regulations of other state and federal government agencies.

II. Background Information and Definitions

1. Radiopharmaceuticals (also known as radioactive drugs) are drugs that contain radionuclides that emit radiation(s). The distribution of the radiopharmaceutical within the body is determined by the physiochemical properties of the drug, the stability of the radiolabel, the purity of the radiopharmaceutical preparation, the pathophysiological state of the patient, and the presence or absence of interfering drugs. Dynamic and static images of the distribution of the radiopharmaceutical within the body can be obtained using a gamma camera, or other suitable instrument appropriate for the radiopharmaceutical being imaged, e.g., positron emitting radiopharmaceuticals. Measurement of radioactivity in specified sites of accumulation or in biological samples following administration of the radiopharmaceutical can be performed for non-imaging procedures. High dose, non-penetrating radiation in localized sites of accumulation of the radiopharmaceutical can be useful for therapeutic procedures.
2. Physiologic and pharmacologic interventions are procedures, which increase the sensitivity and/or specificity of a nuclear medicine procedure by affecting the distribution and pharmacokinetics of the administered agents through an alteration in organ physiology. These procedures will be conducted as outlined in the Nuclear Medicine Procedure Manual 2003-05, which is located in the Nuclear Area in the UAMS Radiology Department.
3. UAMS policy regarding radiopharmaceuticals states that the administration of radioactive materials to patients shall be under the supervision of a physician who has appropriate training and experience and has been approved by the UAMS Radiation Safety Committee. (UAMS policy reference # PS.1.04)

III. Responsibilities and Chain of Command
Principal Investigator: The Principal Investigator (PI) for each human research protocol will be responsible for ensuring that all interventions performed as part of a human research protocol are conducted according to hospital/departmental and IRB guidelines. While the PI’s designees may perform some tasks, the PI is ultimately responsible.

Radiology Staff Responsibilities: The Radiology Research Committee and/or Radiology Research QA/QI will review and approve all protocols involving the Department and provide a written agreement specifying which aspects of care will be provided by Radiology personnel. Trained Radiology personnel will be responsible for registering the subject for the procedure (in the study log book and in the hospital system), maintaining and documenting maintenance of Radiology equipment, performing the procedure, and maintaining the Radiology study binder for each protocol. The Radiology Chief Financial Officer will review and approve the research billing procedure for interventions performed by Radiology prior to the initiation of any research procedure.

Non-Radiology Staff Responsibilities: The Principal Investigator will provide designated study personnel trained in Human Subject Protection (HSP), HIPAA, and the specific protocol. Study personnel will provide all supplies and any additional equipment needed for the study and will inventory supplies with the Radiology personnel prior to the initiation of the study. If Radiology equipment is used, usage time will be approved by the manager for that area prior to the onset of the study. The study personnel provided by the Principal Investigator will accompany the subject through the procedure, providing documentation of signed, informed consent, eligibility, the procedures performed, and the subject’s response to the procedures. The study personnel will document the use of test articles as outlined by the protocol, applicable federal guidelines, state guidelines, and the IRB. Study personnel will provide and document discharge instructions. Copies will be left for the Radiology file. If the Principal Investigator for the study is a UAMS Radiologist, radiology personnel may be trained and designated as the study personnel and assume the responsibilities listed above. Otherwise, these responsibilities will be carried out by qualified non-radiology personnel.

A list of all radiology and non-radiology study personnel, including licensure, qualifications and study responsibilities of each, will be kept with the Radiology study binder. A signature log will also be kept in the Radiology study binder.

IV. Common Indications
Any research protocol which uses a radiopharmaceutical.

V. Procedures

1. Prior to any research intervention involving a radiopharmaceutical, the research protocol will be reviewed, participating staff will be trained, and all protocol activities involving the UAMS Radiology Department will be approved per the UAMS Radiology Research Intervention Policy. The in vivo distribution of radiopharmaceuticals can be altered by concurrent medications and prior diagnostic tests (including contrast dye and previous radiopharmaceuticals). The nuclear medicine practitioner will request a list of documented drug interactions from the Principal Investigator and consider this information prior to planning the nuclear medicine procedure to be performed and when altered distribution patterns are identified on subject studies.
2. A physician-derived order (e.g., prescription, requisition) is required for the conduct of all procedures. The order should specify the procedure desired, the drug(s) to be used, the amount(s) to be administered, the route of administration, and, if applicable, the rate of infusion. Alternately, the order may specify a standard procedure with the required information, i.e., standing orders, specified in the research protocol, a copy of which will be kept within the nuclear medicine laboratory. While the principal investigator will write the order for the test procedure, the nuclear medicine radiologist, trained in the protocol, will write the order for the radiopharmaceutical.
3. The principal investigator, who may or may not be the prescribing physician, is responsible for the overall conduct of the clinical trial. The prescribing nuclear medicine radiologist is ultimately responsible for the dose calculations, safety, quality and correctness of radiopharmaceuticals prepared and dispensed under his (her) supervision. There must be a signed and dated written directive for each subject for all therapeutic radiopharmaceuticals.
4. The preparation, quality control, dispensing and subject administration of radiopharmaceuticals and adjunctive drugs may be delegated to appropriately licensed, trained study personnel, in accordance with applicable state and local laws.
5. The following will be performed and documented in the subject’s clinical and study record:
   • The identity of the radiopharmaceutical, subject and route of administration shall be verified prior to administration. Female subjects who are post-menarche and pre-menopause should be asked about pregnancy, lactation, and breast-feeding prior to administration. A negative pregnancy test in females of childbearing capability will be verified prior to administration of any radiopharmaceutical that could potentially result in a dose to an embryo or fetus of 50 mSv (5 rems) or more (e.g., I-131 therapy).
   • The quantity of each radiopharmaceutical dosage must be determined prior to subject administration and must be consistent with that ordered by the physician, the IRB approved research protocol, or addressed in the procedure manual of the nuclear medicine laboratory. The quantity of radioactivity dispensed should be within 10% of the prescribed dose or dosage range and the actual quantity administered must be recorded in the subject’s medical record. Any discrepancies shall be resolved prior to administration,
   • An additional calculation for the net dose (calculation of radioactivity in the administration set prior to administration less the amount left in the set after administration) for research will be determined and documented in the subject’s medical and study record.
   • Radiopharmaceuticals shall not be used beyond the manufacturer’s recommended expiration date/time unless specific quality control testing demonstrates that the product still meets applicable USP specifications at the time of use.
   • Aseptic procedures must be followed whenever handling parenteral or ophthalmic radiopharmaceutical preparations or their components.
6. Radiopharmaceuticals used in positron emission tomography require specialized personnel, facilities, and equipment due primarily to the relatively short physical half-lives of the radionuclides used (2 min to 1.8 hr), their energetic photon emissions, and the chemical syntheses necessary for their preparation. Preparation of PET radiopharmaceuticals must comply with USP compounding standards or FDA manufacturing requirements.
7. Disposal of all radioactive material must be accomplished in accordance with protocol, institutional, state, and federal regulations. (See UAMS policy reference # MM.2.03 “Removal, Disposal and/or Transfer of Equipment Used with Radioactive Material.”)

VI. Documentation

1. Designated research personnel will provide a complete written record of each study intervention occurring in the Radiology department for each subject. This record will be kept in the subject’s medical record, if applicable, as well as in the subject’s study record. A copy of the subject’s record regarding radiology procedures performed will be kept in the study binder for that protocol. Research subjects will be registered and entered into the appropriate Radiology patient logs at the time of intervention (according to the UAMS Radiology Research Intervention Policy 1.2).
2. Records of receipt, usage, administration, and disposal of all radiopharmaceuticals shall be kept in compliance with license conditions, applicable medical records procedures, radiation control regulations, and procedures outlined in the research protocol. Record retention for radiology procedures done as a part of a research protocol will be determined by the Principal Investigator for that study in accordance with state and federal regulations, any protocol or sponsor requirements, and IRB and institutional policies.
3. Records concerning the receipt of packages containing radioactive material should include proper identification of contents, inspection for physical damage, and testing for external contamination, as required by the appropriate regulatory agency. Appropriate records of the receipt of radioactive material shall be maintained and stored in accordance with applicable IRB and protocol requirements and local, state and federal regulations. Such records shall address the identity of the radiopharmaceutical, its source, the amount of activity received, and the results of radiation surveys and contamination testing. Any discrepancies must be reported to the manufacturer, the IRB, and other proper regulatory agencies.
4. For all radiopharmaceuticals prepared onsite, records will include the date and time of preparation, quantity, volume, and concentration of radioactivity used, net dose delivered, reagent lot numbers, quality control data, expiration time, waste disposal information, and name or initials of the individual responsible for the preparation.
5. For all radiopharmaceuticals, the identity of the radiopharmaceutical, the amount of radioactivity administered, subject identity, identity of individual performing the administration, route of administration, and date and time of use must be recorded. Designated study personnel will record supplies used and operating condition of equipment at the time of each intervention. This record (including the count, amount, receipt, return, destruction, waste, dispensing, handling, storage, labeling, and expiration dates of supplies) will be kept in the study binder. Any discrepancies will be reported immediately to Radiology Research QI/QA, who will report to the PI and develop a plan of action.
6. Appropriate records of radionuclide dose calibrator testing for constancy, accuracy, linearity and geometric variation shall be maintained. Documentation of calibration and maintenance of equipment (as required by hospital/departmental guidelines and/or protocol specifications) will also be kept in the study binder. Equipment logs will be provided by Radiology Research QI/QA personnel and kept up to date by protocol trained personnel according to the guidelines recommended by the Nuclear Medicine Procedure Manual.
7. Case report forms, where applicable will be completed by the designated study personnel and returned to the Principal Investigator according to protocol specifications.
8. Adverse reactions associated with administration of radiopharmaceuticals should be investigated and documented. Reports of serious adverse reactions and product problems should be made to the principle investigator, the IRB, manufacturer and to MedWatch as outlined in the protocol and according to IRB and HIPAA guidelines.
9. Misadministrations, also known as medical events, have been defined by federal and state regulatory agencies and include a timely reporting requirement. When required, such events should be reported to the appropriate agency within the time frame specified. UAMS Policy (reference # ML.1.04 Patient and Visitor Variance Reporting) specifies that medication related events will be monitored by Pharmacy QI and the Pharmacy and Therapeutics Committee as well. While the misadministration of any radiopharmaceutical is serious, special precautions must be implemented to prevent the misadministration of radiopharmaceuticals containing blood products, i.e., Tc-99m red blood cells and In-111 and Tc-99m leukocytes. Procedures which involve the removal of blood for radiolabeling and subsequent reinjection have potential for misadministration to the wrong patient. The Nuclear Medicine Procedure Manual 2003-05 Policy for the Administration of Pharmaceuticals Containing Blood Products is to be followed.

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