[C-11]MDL 100907, a radioligand for selective imaging of 5-HT2A receptors with positron emission tomography

The highly selective 5-HT2A receptor antagonist, MDL 100907 ((R)-(+)-4-(1-hydroxy-1-(2,3-dimethoxyphenyl)methyl)-N-2-(4-fluorophenylethyl)piperidine), was labeled with C-11 for Positron Emission Tomography (PET) studies. After i.v. injection of (R)-(+)-[3-OCH3-C-11]MDL 100907 ([C-11]MDL 100907) in Cynomolgus monkeys a marked accumulation in the 5-HT2A receptor rich neocortical regions was obtained with a neocortex to cerebellum ratio of 3.5-4.5 after 60-80 minutes. In the neocortical regions a transient equilibrium occured within 40-60 minutes. Radioactivity in the neocortex, but not in the cerebellum, was reduced after injection of ketanserin, indicating that neocortical radioactivity following injection of [C-11]MDL 100907 represents specific binding to 5-HT2A receptors. There was no evident effect on neocortical binding after pretreatment with raclopride or SCH 23390. [C-11]MDL 100907 has potential to become the first selective radioligand for PET-quantitation of 5-HT2A receptors in the human brain in vivo.