Positron emission tomography (PET)-microdosing involves giving human subjects a carbon-11- or fluorine-18-labeled drug candidate in microgram amounts to track the drug's concentration over time in targeted body tissues. Because only tiny amounts of unlabeled drug are used, toxicological risk is very low, and regulatory authorities require less preclinical safety testing than for conventional phase 1 studies. Microdose studies are becoming more important in clinical drug research because they can shorten development timelines and reduce costs. The review covers current PET applications in anticancer, anti-infective, and central nervous system drug research.
Systemic absorption of a topically applied drug may not be dose-linear, limiting the usefulness of microdosing to predict therapeutic-dose exposure. In a crossover study of eight healthy participants, a topical microdose of diclofenac (62 μg) resulted in a higher fraction absorbed (0.48%) compared with a therapeutic dose (120 mg, 0.13%), a 3.79-fold difference. Intravenous dosing showed dose-linear disposition. Concentrations in subcutaneous tissue microdialysates were low and variable regardless of dose. The findings indicate that microdosing may not accurately predict the systemic availability of certain topical drugs at therapeutic doses.