RADIOSYNTHESIS OF A NEW RADIOIODINATED LIGAND FOR SEROTONIN-5HT(2)-RECEPTORS, A PROMISING TRACER FOR GAMMA-EMISSION TOMOGRAPHY

4-Amino-N-[1-[3-(4-fluorophenoxy)propyl] -4-methhyl-4-piperidinyl]-2-m ethoxy-benzamide, a compound with high affinity for 5HT(2)-receptors, was radioiodinated on the 2-position of the phenoxygroup or the 5-posi tion of the methoxybenzamide group. The former (obtained by Cu1+-assis ted radioiodo for bromo exchange) showed high lipophilicity and high n on-specific binding to rat brain tissue both in vitro and in vivo. The second labelled compound, I-125-4-amino-N-[1-[3- 4-methyl-4-piperidin yl]-5-iodo-2-methoxybenzamide, obtained by direct electrophilic substi tution, showed high affinity (K-d of 0.11 +/- 0.01 nM) and marked sele ctivity for 5HT(2)-receptors in vitro. Moreover in vivo studies in rat s over the course of 1-3 hrs post i.v. injection of the radioactive li gand, showed steady preferential retention of radioactivity in the fro ntal cortex, which is enriched in 5HT(2) receptors. (Frontal cortex (F C) / Cerebellum ratio of 10 and FC / Blood ratio of 6, amount compound / mg tissue).