SYNTHESIS OF [O-METHYL-C-11]FLUVOXAMINE - A POTENTIAL SEROTONIN UPTAKE SITE RADIOLIGAND

omethyl)-phenyl]-1-pentanone-O-(2-aminoethyl)oxime (fluvoxamine), a po tent clinically used antidepressant, was labelled with carbon-11 (t(1/ 2) = 20.4 min) as a potential radioligand for the non-invasive assessm ent of serotonin uptake sites in the human brain with positron emissio n tomography (PET). The two-step radiochemical synthesis consisted of O-methylation of an amino-protected desmethyl precursor with [C-11]met hyl iodide under mild conditions in the presence of tetrabutylammonium hydroxide in acetonitrile, followed by deprotection with trifluoroace tic acid. omethyl)-phenyl]-1-pentanone-O-(2-aminoethyl)oxime was obtai ned in > 98% radiochemical purity in 40 min with a radiochemical yield of 4 +/- 2% (non-decay corrected) and a specific radioactivity of 1 /- 0.5 Ci/mu mol. y-1-[4-(trifluoromethyl)-phenyl]-1-pemtanone-O-[2- ( tert-butoxycarbonylamino)ethyl] oxime, the precursor for the radiosynt hesis of [C-11]fluvoxamine, was prepared by a convenient three-step sy nthesis from the pharmaceutical form of fluvoxamine maleate by convert ing it into the free base, demethylation by trimethyliodosilane and in troduction of the BOG-protective group with di-tert-butyl dicarbonate. (C) 1997 Elsevier Science Ltd.