In vivo measurement of brain monoamine oxidase B occupancy by rasagiline, using (11)C-l-deprenyl and PET

In recent years, monoamine oxidase B (MAO-B) inhibitors have become widely used in the treatment of early-stage Parkinson's disease. (11)C-l-deprenyl PET has been used by others to characterize MAO-B ligands in terms of their in vivo potency toward MAO-B and duration of action. In this study, we used (11)C-l-deprenyl PET to demonstrate the specific binding characteristics of the new irreversible selective MAO-B inhibitor rasagiline in 3 healthy volunteers. The healthy volunteers received 1 mg of rasagiline daily for 10 d. Dynamic (11)C-l-deprenyl PET brain scans were acquired before the first treatment (scan 1) and immediately (scan 2), 2-3 wk (scan 3), and 4-6 wk (scan 4) after the final treatment. On scan 1, all subjects showed the highest l-deprenyl uptake in the thalamus and basal ganglia, with fairly high activity also in the cortex and cerebellum and much lower activity in the white matter. The areas of high uptake were absent from scan 2, on which activity throughout the brain was comparable to that in white matter, presumably because of blocking of MAO-B binding sites by rasagiline. Gradual recovery toward the baseline state was observed in the weeks after termination of treatment (scans 3 and 4). (11)C-l-deprenyl PET showed binding of rasagiline to MAO-B, confirming blocking of MAO-B sites after 10 d of treatment with 1 mg of rasagiline per day, with immediate post-rasagiline treatment tracer uptake and metabolism in the basal ganglia compatible only with nonspecific binding. Subsequent gradual recovery was also seen, with return to near-baseline uptake. This finding is compatible with the known rate of de novo synthesis of MAO-B, confirming the irreversible binding of rasagiline.