A human [11C]T-773 PET study of PDE10A binding after oral administration of TAK-063, a PDE10A inhibitor

Regional brain uptake was highest in the putamen. Time-activity curves of the brain regions were described with two tissue-compartment (2TC) models. The mean VT was 5.5 ± 0.7 in the putamen and 2.3 ± 0.5 in the cerebellum in the baseline PET. Absolute VT variability between the two baseline scans was less than 7%. Reproducibility of VT was excellent. PDE10A occupancy in the putamen ranged from 2.8% to 72.1% at 3 hours after a single administration of 3 to 1000 mg of TAK-063, and increased in a dose- and plasma concentration-dependent manner. At 23 hours postdose, PDE10A occupancy in the putamen was 0 to 42.8% following administration of 3 to 100 mg of TAK-063. In conclusion, [11C]T-773 showed good characteristics as a PET radioligand for PDE10A in the human brain.