SPECIFIC IN-VIVO BINDING IN THE RAT-BRAIN OF [F-18]RP-62203 - A SELECTIVE 5-HT2A RECEPTOR RADIOLIGAND FOR POSITRON EMISSION TOMOGRAPHY

In vivo pharmacokinetic and brain binding characteristics of [F-18]RP 62203, a selective high-affinity serotonergic 5-HT2A receptor antagoni st, were assessed in the rat following intravenous injection of trace amount of the radioligand. The radioactive distribution profile observ ed in the brain 60 min after injection was characterized by greater th an fourfold higher uptake in neocortex as compared to cerebellum (0.38 +/- 0.07% injected dose/g, % ID/g and 0.08 +/- 0.01 ID/g, respectivel y), consistent with in vivo specific binding to the 5-HT2A receptor. F urthermore, specific [F-18]RP 62203 binding significantly correlated w ith the reported in vitro distribution of 5-HT2A receptors, but not wi th known concentration profiles of dopaminergic D-2 or adrenergic alph a(1) receptors. Finally, detectable specific binding was abolished by pretreatment with large doses of ritanserin, a selective 5-HT2A antago nist, which resulted in uniform uptakes across cortical, striatal and cerebellar tissues. Thus, [F-18]RP 62203 appears to be a promising sel ective tool to visualize and quantify 5-HT2A brain receptors in vivo w ith positron emission tomography.