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

4-Amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidiny l]-2-methoxy-benzamide, a compound with high affinity for 5HT2-receptors, was radioiodinated on the 2-position of the phenoxygroup or the 5-position of the methoxybenzamide group. The former (obtained by Cu1+-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, 125I-4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperid inyl] -5-iodo-2-methoxybenzamide, obtained by direct electrophilic substitution, showed high affinity (Kd of 0.11 ± 0.01 nM) and marked selectivity for 5HT2-receptors in vitro. Moreover in vivo studies in rats over the course of 1-3 hours post i.v. injection of the radioactive ligand, showed steady preferential retention of radioactivity in the frontal cortex, which is enriched in 5HT2-receptors. (Frontal cortex (FC)/Cerebellum ratio of 10 and FC/Blood ratio of 6, amount compound/mg tissue). (author)