title: Synthesis of [O-methyl-11C]fluvoxamine--a potential serotonin uptake site radioligand.
abstract: 5-Methoxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-O-(2-aminoethyl)oxi me (fluvoxamine), a potent clinically used antidepressant, was labelled with carbon-11 (t1/2 = 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-aminoethy l) 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/mumol. 5-Hydroxy-1-[4-(trifluoromethyl)-phenyl]-1-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.
authors.affiliation: CNR-INB, University of Milan, Institute H.S. Raffaele, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Matarrese
authors.forename: D
authors.initials: D
authors.lastname: Soloviev
authors.forename: S
authors.initials: S
authors.lastname: Todde
authors.forename: F
authors.initials: F
authors.lastname: Magni
authors.forename: D
authors.initials: D
authors.lastname: Colombo
authors.forename: M
authors.initials: M
authors.lastname: Galli Kienle
authors.forename: F
authors.initials: F
authors.lastname: Fazio
mesh_terms: D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D016666:Fluvoxamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008722:Methods; D008745:Methylation; D011869:Radioligand Assay; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D016666:Fluvoxamine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C107760:O-methyl-fluvoxamine