SYNTHESES OF [C-11] AND [H-3] LY274601, A SEROTONIN(1A) RECEPTOR AGONIST

LY274601, R-(+)-8-thiomethyl-2-(di-n-propylamino)tetralin, a serotonin (5-HT)(1A) receptor full agonist with high affinity (Ki: 0.6nM) and s electivity, was labeled with C-11 for imaging 5-HT1A receptor sites in vivo by positron emission tomography (PET). [C-11]LY274601 was synthe sized by S-methylation of the normethyl precursor unmasked via hydroly sis of the butyrate thioester of LY274601. The methylation reaction wi th [C-11]iodomethane proceeded quickly and efficiently in DMF at 40 de grees 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/mu mol at the end of synthesis (E.O.S.). Th is labeling procedure was also employed in the preparation of [H-3]LY2 74601, R-(+)-8-[H-3]methylthio-2-(di-n-propyl -amino)tetralin, from [H -3]iodomethane.