Short Communication 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 sen- sitivity of the positron emission tomography (PET) radioligand ( 11 C)P943 to fen- fluramine-induced changes in endogenous 5-HT in nonhuman primate brain. Fen- fluramine-induced changes in 5-HT1B 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 occu- pancy 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-HT1B receptors with ( 11 C)P943 may be a useful approach for measuring changes in endogenous 5-HT in the living human brain. Synapse 65:1113-1117, 2011. V C 2011 Wiley-Liss, Inc.

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