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

Appl Radiat Isot. 1997 Jun;48(6):749-54. doi: 10.1016/s0969-8043(96)00304-1.

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.

MeSH terms

  • Binding Sites
  • Brain / metabolism
  • Carbon Radioisotopes
  • Fluvoxamine / analogs & derivatives*
  • Fluvoxamine / chemical synthesis
  • Fluvoxamine / metabolism
  • Fluvoxamine / pharmacology
  • Humans
  • Methods
  • Methylation
  • Radioligand Assay
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis*
  • Selective Serotonin Reuptake Inhibitors / metabolism
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / metabolism
  • Tomography, Emission-Computed

Substances

  • Carbon Radioisotopes
  • O-methyl-fluvoxamine
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Fluvoxamine