the binding of drug candidates to target and non-target tissues can be determined with relative ease and tissue pharmacokinetics can be studied. Furthermore, with targeted radiotracers, the efficiency of target occupancy and inhibition can be assessed non-invasively. Based on these animal data, imaging biomarkers can be developed to monitor treatment effects and to determine optimal drug doses on a molecular level in clinical studies. The small imaging devices also offer a means for rapid screening of potential drug candidates. For example, the effects of novel compounds on cell proliferation or cell metabolism can be determined in small-animal tumor models with fluorine-18-FLT and fluorine-18-FDG and thus serve as a “generic pharmacodynamic readout” (Leyton et al. 2005).
As described above, nuclear medicine imaging has the potential to further improve patient care in a variety of ways. However, the actual number of new radiotracers introduced into clinical practice over the past 10 years has been very limited. For example, although this chapter discusses a significant number of PET agents, only one agent (FDG) is used in more than 95 percent of all clinical PET studies. It is clear that the transfer of promising radiopharmaceutical and molecular probes from small animals to humans faces considerable hurdles. In part, this reflects the uncertain path that any drug must follow as it goes from discovery into application. For radiopharmaceuticals there are the added economic concerns of the relatively small market, even for common indications such as cancer. Some specific barriers are listed below.
Regulatory Impediments. Taken together, the regulatory impediments that limit approval and reimbursement for novel radiopharmaceuticals are the most important barrier to the continuing development and introduction of novel radiopharmaceuticals into clinical nuclear medicine practice. For example, the 1997 FDA Modernization Act, and the congressional and regulatory action that accompanied the enacting of this legislation, made possible the implementation of FDG-PET imaging as a clinical reality. A time table was proposed in the act, according to which more complete regulatory guidance should have been developed by the Food and Drug Administration (FDA) for facilitated regulation within 2 years. We are at the 10-year mark now, and no new regulation has yet been enacted to deal with the special features required for review and approval, or with clearance for reimbursement of novel nuclear medicine imaging procedures. This lack of clarity about process limits incentive to develop new agents and discourages commercial investment. It would be helpful if more spe-