Synthesis and in vivo imaging properties of [11C]befloxatone: a novel highly potent positron emission tomography ligand for mono-amine oxidase-A

Bioorg Med Chem Lett. 2003 May 19;13(10):1771-5. doi: 10.1016/s0960-894x(03)00215-4.

Abstract

Befloxatone (1, (5R)-5-(methoxymethyl)-3-[4-[(3R)-4,4,4-trifluoro-3-hydroxybutoxy]phenyl]-2-oxazolidinone) is an oxazolidinone derivative belonging to a new generation of reversible and selective mono-amine oxidase-A (MAO-A) inhibitors. In vitro and ex vivo studies have demonstrated that befloxatone is a potent, reversible and competitive MAO-A inhibitor with potential antidepressant properties. Befloxatone (1) was labelled with carbon-11 (t(12): 20.4 min) using [(11)C]phosgene as reagent. Typically, starting from a 1.2 Ci (44.4 GBq) cyclotron-produced [(11)C]CH(4) batch, 150-300 mCi (5.55-11.10 GBq) of [(11)C]befloxatone ([(11)C]-1) with a radiochemical- and chemical purity of more than 99% were routinely obtained within 20 min of radiosynthesis (including HPLC purification) with specific radioactivities of 500-2000 mCi/micromol (18.5-74.0 GBq/micromol). The results obtained in vivo with carbon-11-labelled befloxatone not only confirm the biochemical and pharmacological profile of befloxatone found in rodent and in human tissues but also point out [(11)C]befloxatone as an excellent tool for the assessment of MAO-A binding sites using positron emission tomography, a high-resolution, sensitive, non-invasive and quantitative imaging technique.

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Carbon Radioisotopes / pharmacokinetics*
  • Ligands
  • Monoamine Oxidase / analysis
  • Monoamine Oxidase Inhibitors* / chemical synthesis
  • Monoamine Oxidase Inhibitors* / pharmacokinetics
  • Oxazoles / chemical synthesis
  • Oxazoles / pharmacokinetics*
  • Papio
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution
  • Tomography, Emission-Computed / methods*

Substances

  • Carbon Radioisotopes
  • Ligands
  • Monoamine Oxidase Inhibitors
  • Oxazoles
  • Radiopharmaceuticals
  • befloxatone
  • Monoamine Oxidase