Macaque brain PET study on [11C]ASP0777, an non-competitive NMDA receptor antagonist

1816 Objectives ASP0777 is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist as a drug candidate for the treatment of moderate to severe Alzheimer’s disease. The present study was undertaken to confirm brain penetration of [11C]ASP0777 in conscious rhesus macaques. Methods Three male rhesus macaques (6-10 y; 6.850-8.490 kg) were subjected. [11C]ASP0777 was administered either at the dose of tracer alone, 0.1, or 1 mg/kg, and each animal was studied for all doses. A dynamic PET scan of 90 min was performed following an intravenous injection of [11C]ASP0777. Arterial blood samples were collected while PET scanning to measure the ASP0777 concentration in the plasma, which were corrected for metabolites using thin layer chromatography (TLC). Brain distribution was calculated for 12 brain regions as standardized uptake value (SUV), and ASP0777 concentration was calculated according to the specific activity of ASP0777 preparation. Results [11C]ASP0777 showed a good brain penetration and relatively higher uptake in the striatum (SUV = 1.99, brain/plasma = 23.29, at 1 h, tracer dose) and the thalamus (SUV = 2.01, brain/plasma = 23.67, at 1 h, tracer dose). ASP0777 also showed a linear relationship between the dose and brain concentration for all doses tested. Conclusions The penetration of [11C]ASP0777 into the monkey brain could be confirmed which brings useful information for drug discovery research as a kind of pharmacokinetic study.