Assessing the sensitivity of [ 11 C]p943, a novel 5‐HT IB radioligand, to endogenous serotonin release

The main objective of the current study was to determine the sensitivity of the positron emission tomography (PET) radioligand [ 11 C]P943 to fenfluramine‐induced changes in endogenous 5‐HT in nonhuman primate brain. Fenfluramine‐induced changes in 5‐HT 1B occupancy were compared to those obtained by self‐block with unlabeled P943. Two baboons and 1 rhesus monkey were given preblocking or displacing doses of fenfluramine (1–5 mg/kg) or preblocking doses of unlabeled P943 (0.2 mg/kg) and imaged with [ 11 C]P943 PET. Receptor occupancy by the low dose of fenfluramine (1 mg/kg) in the baboons was 25 and 29% and by the high dose of fenfluramine (5 mg/kg) in the rhesus macaque was 42%. Receptor occupancy by P943 (0.2 mg/kg) was 68 and 86% in the baboons. PET imaging of 5‐HT 1B receptors with [ 11 C]P943 may be a useful approach for measuring changes in endogenous 5‐HT in the living human brain. Synapse, 2011. © 2011 Wiley‐Liss, Inc.