Bush__The_Essential_Physics_for_Medical_Imaging - Biomedical ...

depending on the solvent, either remain at the origin (Rr = 0) or move with the solventfront to the end of the strip (Rr = 1). For example, with a silica stationary phasein an acetone solvent, Tc-99m-MAA remains at the origin and any free pertechnetateor hydrolyzed T c-99m moves with the solvent front. On the other hand, 1-131(as bound Nal) moves with the solvent front (Rr = 1) in an 85% methanol solvent,while the impurity (unbound iodine) moves ~20% of the distance from the origin(Rr = 0.2). These assays are easy to perform and should be used as part of a routineradiopharmacy quality control program and whenever there is a question about theradiochemical integrity of a radiopharmaceutical preparation.19.3 REGULATORY ISSUESInvestigationalRadiopharmaceuticalsAll pharmaceuticals for human use, whether radioactive or not, are regulated by theU.S. Food and Drug Administration (FDA). A request to evaluate a new radiopharmaceuticalfor human use is submitted to the FDA in an application called a"Notice of Claimed Investigational Exemption for a New Drug" (IND). The INDcan be sponsored by either an individual physician or a radiopharmaceutical manufacturerwho will work with a group of clinical investigators to collect the necessarydata. The IND application includes the names and credentials of the investigators,the clinical protocol, details of the research project, details of themanufacturing of the drug, and animal toxicology data. The clinical investigationof the new radiopharmaceutical occurs in three stages. Phase I focuses on a limitednumber of patients and is designed to provide information on the pharmacologicdistribution, metabolism, dosimetry, toxicity, optimal dose schedule, and adversereactions. Phase II studies include a limited number of patients with specific diseasesto begin the assessment of the drug's efficacy, refine the dose schedule, and collectmore information on safety. Phase III clinical trials involve a much larger numberof patients (and are typically conducted by several institutions) to provide moreextensive (i.e., statistically significant) information on efficacy, safety, and doseadministration. To obtain approval to market a new radiopharmaceutical, a "NewDrug Application" (NDA) must be submitted to and approved by the FDA.Approval of a new radiopharmaceutical typically requires 5 to 10 years from laboratorywork to NDA. The package insert of an approved radiopharmaceuticaldescribes the intended purpose of the radiopharmaceutical, the suggested dose,dosimetry, adverse reactions, clinical pharmacology, and contraindications.Regulatory agencies require that all research involving human subjects bereviewed and approved by an institutional review board (IRB) and that informedconsent be obtained from each research subject. Most academic institutions haveIRBs. An IRB comprises clinical, scientific, legal, and other experts and mustinclude at least one member who is not otherwise affiliated with the institurion.Informed consent must be sought in a manner that minimizes the possibility ofcoercion and provides the subject sufficient opportunity to decide whether or notto participate. The information presented must be in language understandable tothe subject. It must include a statement that the study involves research, the purposesof the research, a description of the procedures, and identification of any proceduresthat are experimental; a description of any reasonably foreseeable risks ordiscomforts; a description of any likely benefits to the subject or to others; a dis-