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 (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.
Dolle
Frédéric
F
Service Hospitalier Frédéric Joliot, Département de Recherche Médicale, CEA/DSV, 4 place du Général Leclerc, F-91406 Orsay, France. dolle@dsvidf.cea.fr
Valette
Héric
H
Bramoulle
Yann
Y
Guenther
Ilonka
I
Fuseau
Chantal
C
Coulon
Christine
C
Lartizien
Carole
C
Jegham
Samir
S
George
Pascal
P
Curet
Olivier
O
Pinquier
Jean-Louis
JL
Bottlaender
Michel
M
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D008024:Ligands; D008995:Monoamine Oxidase / Q000032:analysis; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D010080:Oxazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D010215:Papio; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
D002250:Carbon Radioisotopes; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D019275:Radiopharmaceuticals; C090014:befloxatone; D008995:Monoamine Oxidase