In vivo Quantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]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.