Within-subject comparison of 11C-()-PHNO and 11 Craclopride sensitivity to acute amphetamine challenge in healthy humans

Abstract

11 CPHNO is a D 2/D 3 agonist positron emission tomography radiotracer, with higher in vivo affinity for D 3 than for D 2 receptors. As 11C-(+)-PHNO is an agonist, its in vivo binding is expected to be more affected by acute fluctuations in synaptic dopamine than that of antagonist radiotracers such as 11Craclopride. In this study, the authors compared the effects of an oral dose of the dopamine releaser amphetamine (0.3 mg/kg) on in vivo binding of 11C-(+)-PHNO and 11Craclopride in healthy subjects, using a within-subjects, counterbalanced, open-label design. In the dorsal striatum, where the density of D 3 receptors is negligible and both tracers predominantly bind to D 2 receptors, the reduction of 11C-(+)-PHNO binding potential (BP ND) was 1.5 times larger than that of 11Craclopride. The gain in sensitivity associated with the agonist 11C-(+)-PHNO implies that 65% of D 2 receptors are in the high-affinity state in vivo. In extrastriatal regions, where 11C-(+)-PHNO predominantly binds to D 3 receptors, the amphetamine effect on 11C-(+)- PHNO BP ND was even larger, consistent with the higher affinity of dopamine for D 3. This study indicates that 11C-(+)-PHNO is superior to 11Craclopride for studying acute fluctuations in synaptic dopamine in the human striatum. 11C-(+)-PHNO also enables measurement of synaptic dopamine in D 3 regions. © 2012 ISCBFM All rights reserved.