Synthesis of [O-methyl-C-11]fluvoxamine - A potential serotonin uptake site radioligand

5-Methoxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-O-(2- aminoethyl)oxime (fluvoxamine), a potent clinically used antidepressant, was labelled with carbon-11 (t(1/2) = 20.4 min) as a potential radioligand for the non-invasive assessment of serotonin uptake sites in the human brain with positron emission tomography (PET). The two-step radiochemical synthesis consisted of O-methylation of an amino-protected desmethyl precursor with [11C]methyl iodide under mild conditions in the presence of tetrabutylammonium hydroxide in acetonitrile, followed by deprotection with trifluoroacetic acid. 5-[11C]Methoxy-1-[4-(trifluoromethyl)-phenyl]-1- pentanone-O-(2-aminoethyl)oxime was obtained 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/μmol. 5-Hydroxy-l-[4- (trifluoromethyl)-phenyl]-l-pentanone-O-[2(tert- butoxycarbonylamino)ethyl]oxime, the precursor for the radiosynthesis of [11C]fluvoxamine, was prepared by a convenient three-step synthesis from the pharmaceutical form of fluvoxamine maleate by converting it into the free base, demethylation by trimethyliodosilane and introduction of the BOC- protective group with di-tert-butyl dicarbonate.