Carbon-11 labelling of eticlopride in two different positions—a selective high-affinity ligand for the study of dopamine D-2 receptors using PET

Abstract

A new highly selective high-affinity dopamine D-2 receptor antagonist, eticlopride ((−)-(S)-5-chloro-3-ethyl- N-((1-ethyl-2-pyrrolidinyl)methyl)-6-methoxysalicylamide), was labelled with 11C in two different positions ([ N-ethyl- 11C]eticlopride ( I)) and ([methyl- 11C]eticlopride ( II)). Product I was prepared by N-alkylation of the N-desethyl compound with [ 11C]ethyl iodide. II was prepared by O-alkylation of the diphenolic precursor with [ 11C]methyl iodide followed by separation of the two methylated products. The radiochemical yields were 15–20% (EOB) with an overall synthesis time of 45–60 min. Both compounds were isolated by semi-preparative HPLC and the radiochemical purity was in both cases >99%. I was injected i.v. in a Cynomolgus monkey and brain radioactivity was measured by positron emission tomography (PET). The specific activity was 70 Ci/mmol at time of injection. There was a marked accumulation of radioactivity in the basal ganglia, regions known to have a high density of dopamine D-2 receptors.