11C-MP-10 is a suitable radiotracer for PET imaging of phosphodiesterase 10A (PDE10A)

361 Objectives We have previously demonstrated the capability of 11C-MP-10 to image PDE10A in baboons with reversible kinetics and high specific binding signals1. Accurate quantification requires negligible radiolabeled metabolites in the brain. However, a study in rhesus monkeys indicated that 11C-MP-10 displayed irreversible uptake kinetics attributable to the presence of a radiolabeled metabolite in the brain2. This study addressed these discrepancies in rhesus monkeys. Methods Ex vivo studies in one rhesus monkey and 4 rats were performed to investigate radioactivity profile in the brain 45 or 60 min after 11C-MP-10 injection (305 MBq and 30.9±6.3 MBq, respectively). PET scans were performed in rhesus monkeys (mean injected activity and mass doses of 142 MBq and 0.018 μg/kg, respectively, n = 6) on the FOCUS-220 scanner to assess baseline kinetics (n=3), and binding specificity with pretreatment of unlabeled MP-10 (0.1, 0.3 or 0.6 mg/kg). Metabolite-corrected arterial input function was measured for all scans. Imaging data were analyzed with kinetic models to estimate regional volume of distribution (VT). Results The ex vivo studies confirmed specific binding of 11C-MP-10 in the striatum, with no or negligible radiolabeled metabolites in the frontal cortex, striatum, and cerebellum of both species. In rhesus monkeys, 11C-MP-10 displayed reversible uptake kinetics, although clearance appeared to be slower than in baboons. 11C-MP-10 uptake in PDE10A-rich brain regions was decreased in a dose-dependent manner when the monkeys were pretreated with unlabeled MP-10. The multilinear analysis (MA1) method proved to be the most appropriate for estimation of VT values. Conclusions PET scans with 11C-MP-10 in rhesus monkeys demonstrated tissue kinetics and specific binding signals consistent with our previous observations in baboons1. Little or no radioactive metabolites were found in the brain of monkey or rat. Hence, our current results strongly support the suitability of 11C-MP-10 for PET imaging and quantification of PDE10A.