In vivo quantification of monoamine oxidase A in baboon brain: a PET study using [(11)C]befloxatone and the multi-injection approach.
[(11)C]befloxatone is a high-affinity, reversible, and selective radioligand for the in vivo visualization of the monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET). The multi-injection approach was used to study in baboons the interactions between the MAO-A binding sites and [(11)C]befloxatone. The model included four compartments and seven parameters. The arterial plasma concentration, corrected for metabolites, was used as input function. The experimental protocol-three injections of labeled and/or unlabeled befloxatone-allowed the evaluation of all the model parameters from a single PET experiment. In particular, the brain regional concentrations of the MAO-A binding sites (B'(max)) and the apparent in vivo befloxatone affinity (K(d)) were estimated in vivo for the first time. A high binding site density was found in almost all the brain structures (170+/-39 and 194+/-26 pmol/mL in the frontal cortex and striata, respectively, n=5). The cerebellum presented the lowest binding site density (66+/-13 pmol/mL). Apparent affinity was found to be similar in all structures (K(d)V(R)=6.4+/-1.5 nmol/L). This study is the first PET-based estimation of the B(max) of an enzyme.
Bottlaender
Michel
M
CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, 4, place du Général Leclerc, F-91401 Orsay, France. michel.bottlaender@cea.fr
Valette
Héric
H
Delforge
Jacques
J
Saba
Wadad
W
Guenther
Ilonka
I
Curet
Olivier
O
George
Pascal
P
Dollé
Frédéric
F
Grégoire
Marie-Claude
MC
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000201:enzymology; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000378:metabolism; D010080:Oxazoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D010215:Papio / Q000033:anatomy & histology / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology
D002250:Carbon Radioisotopes; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D019275:Radiopharmaceuticals; C090014:befloxatone; D008995:Monoamine Oxidase