title: [(11)C]SL25.1188, a new reversible radioligand to study the monoamine oxidase type B with PET: preclinical characterisation in nonhuman primate.
abstract: [(11)C]SL-25.1188 [(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[d]isoxazol-3-yl]-oxazolidin-2-one], an oxazolidinone derivative, was characterized in baboons as a radioligand for the in vivo visualization of MAO-B using positron emission tomography (PET). After i.v. injection, [(11)C]SL25.1188 presented a rapid phase of distribution in blood (about 5 min), followed by a T(1/2) elimination of 85 +/- 14 min. Plasma metabolism analysis showed that [(11)C]SL25.1188 is stable in vivo at least for 30 min. Brain uptake was rapid with the highest one observed in the striatum and thalamus, and the lowest in the pons. Calculated distribution volumes (V(T)) were as follows: striatum = 10.3, thalamus = 10.9, hippocampus = 8.9, temporal cortex = 7.7, occipital cortex = 7.2, parietal cortex = 7.4, frontal cortex = 7.4, white matter = 7.4, and pons = 6.1. Pretreatment with deprenyl (2 mg/kg, i.v.) or lazabemide (0.5 mg/kg, i.v.) reduced V(T) values in all brain areas up to 50%. In displacement experiments, injection of SL25.1188 or deprenyl (1 and 2 mg/kg, i.v., respectively) strongly reduced the specific uptake of [(11)C]SL25.1188 in all brain areas (85-100%), while a lesser displacement was observed with lazabemide (0.5 mg/kg, i.v.) (55-70% of specific binding depending on the brain area). Therefore, [(11)C]SL25.1188 is characterized in vivo by reversible binding, high brain uptake and very slow plasma metabolism, strongly suggesting that this radioligand is a potent tool for the in vivo study of brain MAO-B.
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Orsay F-91401, France. wadad.saba@cea.fr
authors.forename: Wadad
authors.initials: W
authors.lastname: Saba
authors.forename: Héric
authors.initials: H
authors.lastname: Valette
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Peyronneau
authors.forename: Yann
authors.initials: Y
authors.lastname: Bramoullé
authors.forename: Christine
authors.initials: C
authors.lastname: Coulon
authors.forename: Olivier
authors.initials: O
authors.lastname: Curet
authors.forename: Pascal
authors.initials: P
authors.lastname: George
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D023303:Oxazolidinones / Q000493:pharmacokinetics*; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
chemical_list: D023303:Oxazolidinones; D019275:Radiopharmaceuticals; D008995:Monoamine Oxidase