Synthesis, radiolabeling and biological evaluation of [125I]-1-[2-(benzylthio)ethyl]-4-(5-iodo-2-methoxyphenyl)piperazine as a new 5-HT1A receptor ligand

Abstract

Abstract 5-HT1A receptors have been implicated in the pathogenesis of a wide variety of disorders related to the serotonin receptors. WAY100635 is a well-known high affinity 5-HT1A receptor antagonist. Many 11C and 18F radiolabeled derivatives and its radioiodinated analogues have been reported as imaging agents for 5-HT1A receptors. In this regard, the synthesis, radiolabeling and biological evaluation of a new 5-HT1A receptor radioligand, [125I]-1-(2-(benzylthio)ethyl)-4-(5-iodo-2-methoxyphenyl)piperazine ([125I]-BTE-IMPP), are described. Radioiodination of this newly synthesized compound was done by the direct aromatic electrophilic substitution via Iodo-Gen method. Radiochemical yield and radiochemical purity determined by TLC and RTLC were >70% and >95%, respectively. Biodistribution studies of [125I]-BTE-IMPP in rats displayed relatively high uptake in hippocampus (Hip) and low uptake in cerebellum (Cer). The level of the radiotracer uptake was over threefold higher in hippocampus than in cerebellum at 30 min post-injection. Moreover, the brain to blood uptake ratio and the blocking studies results indicated prolonged retention of the radiotracer and relatively good specific binding to 5-HT1A receptor. These findings strongly suggest that [125I]-BTE-IMPP could be a good candidate as an in vivo marker for pharmacological study of 5-HT1A receptors in animal models.