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

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 (t1/2: 20.4 min) using [11C]phosgene as reagent. Typically, starting from a 1.2 Ci (44.4 GBq) cyclotron-produced [11C]CH4 batch, 150–300 mCi (5.55–11.10 GBq) of [11C]befloxatone ([11C]-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/μmol (18.5–74.0 GBq/μmol). 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 [11C]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.