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

Abstract

[11 C] 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 [11 C] 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). [11 C] 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. [11 C] P943 shows promise as a tracer to image serotonin function in healthy subjects as well as subjects with psychiatric or neurologic conditions.