Vol. 305, Issue 2, 467-473, May 2003

Mapping the Cerebral Monoamine Oxidase Type A: Positron Emission Tomography Characterization of the Reversible Selective Inhibitor [¹¹C]Befloxatone

Michel Bottlaender, Frédéric Dollé, Ilonka Guenther, Dimitri Roumenov, Chantal Fuseau, Yann Bramoulle, Olivier Curet, Jamir Jegham, Jean-Louis Pinquier, Pascal George and Heric Valette

Commissariat à l'Energie Atomique, Service Hospitalier Frédéric Joliot, Département de Recherche Médicale/Direction des Sciences du Vivant, Orsay, France (M.B, F.D., I.G., D.R., C.F., Y.B., H.V.); and Sanofi-Synthélabo Recherche, Bagneux, France (O.C., J.J., J.-L.P., P.G.)

Befloxatone is a competitive and reversible inhibitor of monoamine oxidase-A (MAOI-A). The aim of the study was to characterize the in vivo properties of [¹¹C]befloxatone and to validate its use as a ligand for the study of MAO-A by positron emission tomography (PET). PET studies were performed in baboons after i.v. injection of [¹¹C]befloxatone (551 ± 70 MBq, i.e.14.9 ± 1.9 mCi). [¹¹C]Befloxatone enters rapidly in the brain with a maximum uptake at 30 min. Brain concentration of the tracer is high in thalamus, striatum, pons and cortical structures (1.5-1.8% of injected dose per 100 ml of tissue), and lower in cerebellum (1.07% injected dose/100 ml). Nonsaturable uptake, obtained after a pretreatment with a high dose of nonlabeled befloxatone (0.4 mg/kg), is very low and represents only 3% of the total uptake. Brain uptake of [¹¹C]befloxatone is not altered by a pretreatment of a high dose with lazabemide (0.5 mg/kg i.v.), a selective MAOI-B but is completely blocked by a pretreatment with moclobemide (MAOI-A; 10 mg/kg). This confirms, in vivo, the selectivity of befloxatone for type A MAO. [¹¹C]Befloxatone brain radioactivity was displaced by administration of unlabeled befloxatone (30 min after the tracer injection). The displacement of the tracer from its binding sites is dose-dependent, with an ID₅₀ of 0.02 mg/kg for all studied structures. These results indicate that [¹¹C]befloxatone will be an excellent probe for the study of MAO-A in humans using PET.