Within-Subject Comparison Of [C-11]-(+)-Phno And [C-11]Raclopride Sensitivity To Acute Amphetamine Challenge In Healthy Humans

[C-11]PHNO 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 [C-11]-(+)-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 [C-11] raclopride. 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 [C-11]-(+)-PHNO and [C-11] raclopride 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 [C-11]-(+)-PHNO binding potential (BPND) was 1.5 times larger than that of [C-11] raclopride. The gain in sensitivity associated with the agonist [C-11]-(+)-PHNO implies that similar to 65% of D-2 receptors are in the high-affinity state in vivo. In extrastriatal regions, where [C-11]-(+)-PHNO predominantly binds to D-3 receptors, the amphetamine effect on [C-11]-(+)-PHNO BPND was even larger, consistent with the higher affinity of dopamine for D-3. This study indicates that [C-11]-(+)-PHNO is superior to [C-11] raclopride for studying acute fluctuations in synaptic dopamine in the human striatum. [C-11]-(+)-PHNO also enables measurement of synaptic dopamine in D-3 regions. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 127-136; doi:10.1038/jcbfm.2011.115; published online 31 August 2011