Radiosynthesis of a new radioiodinated ligand for serotonin‐5HT₂‐receptors, a promising tracer for γ‐emission tomography

Abstract

Abstract 4‐Amino‐N‐[1‐[3‐(4‐fluorophenoxy)propyl]‐4‐methyl‐4‐piperidinyl]‐2‐methoxy‐benzamide, a compound with high affinity for 5HT 2 ‐receptors, was radioiodinated on the 2‐position of the phenoxygroup or the 5‐position of the methoxybenzamide group. The former (obtained by Cu 1+ ‐assisted radioiodo for bromo exchange) showed high lipophilicity and high non‐specific binding to rat brain tissue both in vitro and in vivo. The second labelled compound, 125 I‐4‐amino‐N‐[1‐[3‐(4‐fluorophenoxy)propyl]‐4‐methyl‐4‐piperidinyl]‐5‐iodo‐2‐methoxybenza‐mide, obtained by direct electrophilic substitution, showed high affinity (K d of 0.11 ± 0.01 nM) and marked selectivity for 5HT 2 ‐receptors in vitro. Moreover in vivo studies in rats over the course of 1‐3 hrs post i.v. injection of the radioactive ligand, showed steady preferential retention of radioactivity in the frontal cortex, which is enriched in 5HT 2 receptors. (Frontal cortex (FC) / Cerebellum ratio of 10 and FC / Blood ratio of 6, amount compound / mg tissue).