Mapping the cerebral monoamine oxidase type A: positron emission tomography characterization of the reversible selective inhibitor [11C]befloxatone.
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 [(11)C]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 [(11)C]befloxatone (551 +/- 70 MBq, i.e.14.9 +/- 1.9 mCi). [(11)C]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 [(11)C]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. [(11)C]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 ID(50) of 0.02 mg/kg for all studied structures. These results indicate that [(11)C]befloxatone will be an excellent probe for the study of MAO-A in humans using PET.
Bottlaender
Michel
M
Commissariat à l'Energie Atomique, Service Hospitalier Frédéric Joliot, Département de Recherche Médicale/Direction des Sciences du Vivant, Orsay, France. bottlaen@shfj.cea.fr
Dolle
Frederic
F
Guenther
Ilonka
I
Roumenov
Dimitri
D
Fuseau
Chantal
C
Bramoulle
Yann
Y
Curet
Olivier
O
Jegham
Jamir
J
Pinquier
Jean-Louis
JL
George
Pascal
P
Valette
Heric
H
D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000000981:diagnostic imaging* / Q000201:enzymology*; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D010080:Oxazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D010215:Papio; D014055:Tomography, Emission-Computed
D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; C090014:befloxatone; D008995:Monoamine Oxidase