Characterization of in vivo pharmacological properties and sensitivity to endogenous serotonin of [11C] P943: A positron emission tomography study in Papio anubis

[11C] P943 is a recently developed PET radiotracer for serotonin 5‐HT1B receptors. We characterized a number of its in vivo pharmacokinetic properties, including the evaluation of its two stereo‐isomers, saturability of specific binding, selectivity for 5‐HT1B and 5‐HT1D receptors, and vulnerability to pharmacologically induced increases in endogenous 5‐HT levels. Six isoflurane‐anesthetized baboons were scanned with [11C] P943 at baseline, and following various pharmacological manipulations. The interventions included the administration of pharmacological doses of P943, SB‐616234‐S (a 5‐HT1B selective antagonist), SB‐714786 (a 5‐HT1D selective antagonist), as well as the administration of 5‐HT releasing agents (fenfluramine, amphetamine) and 5‐HT reuptake inhibitor (citalopram). [11C] P943 was observed to bind saturably and specifically to 5‐HT1B receptors and to be sensitive to all three challenges known to alter 5‐HT levels in the proximity of receptors. [11C] P943 shows promise as a tracer to image serotonin function in healthy subjects as well as subjects with psychiatric or neurologic conditions. Synapse, 2011. © 2011 Wiley‐Liss, Inc.