Syntheses of [11C] and [3H] LY274601, a serotonin1A receptor agonist

Abstract

LY274601, R-(+)-8-thiomethyl-2-(di-n-propylamino)tetralin, a serotonin (5-HT) 1A receptor full agonist with high affinity (Ki: 0.6nM) and selectivity, was labeled with 11 C for imaging 5-HT 1A receptor sites in vivo by positron emission tomography (PET). [ 11 C]LY274601 was synthesized by S-methylation of the normethyl precursor unmasked via hydrolysis of the butyrate thioester of LY274601. The methylation reaction with [ 11 C]iodomethane proceeded quickly and efficiently in DMF at 40°C, yielding the radiotracer in an average overall radiochemical yield of 35.7±9.8%, The synthesis time including HPLC purification and formulation for injection was approximately 30 min. The specific activity was 630±78mCi/μmol at the end of synthesis (E.O.S.). This labeling procedure was also employed in the preparation of [ 3 H]LY274601, R-(+)-8-[ 3 H]methylthio-2-(di-n-propyl-amino)tetralin, from [ 3 H]iodomethane.