In vivo quantification of monoamine oxidase A in baboon brain: a PET study using [C-11]befloxatone and the multi-injection approach.

[C-11]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 [C-11] 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 (KdVR = 6.4 +/- 1.5 nmol/L). This study is the first PET-based estimation of the B-max of an enzyme. © 2010, Nature Publishing Group