抄録
The PET microdose technique is a pharmacokinetic study, in which the subject is administered with a drug candidate compound labeled with a positron emitter (11C or 18F) and the distribution and time course of radioactivity is measured with a PET camera. The labeled compound can also be given in a therapeutic dose. Together with blood sampling and metabolite analysis, the pharmacokinetics of the entire body can be examined. It is the only way to directly measure organ pharmacokinetics in human subjects and it is useful to measure the intracerebral concentration of a compound, which often has a large species variation. However, there are some limitations. Because 11C is too short-lived (half life=20 min), the compound should contain fluorine that can be labeled with 18F (half life=110 min) efficiently. Although formulation is an important factor for absorption, the labeled compound is usually given in a water solution in the case of oral administration, which may result in different absorption kinetics from that of capsules and tablets. Also radiation exposure to the alimentary tract cannot be ignored if a radioactive compound is orally administered. Considering those limitations, more researchers and drug companies are developing PET probes to image specific transporters and drug targets, which can be used to evaluate specific drug transport systems, to select subjects, or to measure receptor occupancy and other pharmacological effects of a candidate compound given in a therapeutic dose. Because of small mass dose, eIND and other microdose approaches are available for the clinical development of such PET probes to be used as diagnostics.
