In vivo quantification of monoamine oxidase A in baboon brain: A PET study using 11Cbefloxatone and the multi-injection approach

Abstract

11Cbefloxatone 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 11Cbefloxatone. The model included four compartments and seven parameters. The arterial plasma concentration, corrected for metabolites, was used as input function. The experimental protocolthree injections of labeled andor unlabeled befloxatoneallowed 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±26pmolmL in the frontal cortex and striata, respectively, n5). The cerebellum presented the lowest binding site density (66±13pmolmL). Apparent affinity was found to be similar in all structures (KdV R6.4=±1.5nmolL). This study is the first PET-based estimation of the B(max) of an enzyme. © 2010 ISCBFM All rights reserved.