In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach

Abstract

[ 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 0 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.

Relationship of Monoamine Oxidase-A Distribution Volume to Postpartum Depression and Postpartum Crying

“…Finally, the specific binding of [ 11 C]-harmine represents both MAO-A density and affinity since an increase in either could increase [ 11 C]-harmine binding. A change in affinity is unlikely since affinity is similar across brain regions (Bottlaender et al, 2010), and, to the best of our knowledge, MAO-A affinity has not been reported to be modifiable in brain tissue. However, even if affinity of MAO-A alone were increased, this would not necessarily change the functional interpretation of our data as greater affinity of MAO-A for substrate could still represent a mechanism for increased monoaminergic loss and excessive oxidation.…”

Lower Monoamine Oxidase-A Total Distribution Volume in Impulsive and Violent Male Offenders with Antisocial Personality Disorder and High Psychopathic Traits: An [11C] Harmine Positron Emission Tomography Study

“…MAO-A V T represents the total tissue binding of [ 11 C] harmine at equilibrium and is highly correlated with MAO-A level, as would be expected since in vivo MAO-A affinity is similar across regions in primates (Bottlaender et al, 2010). Both the unconstrained two-tissue compartment model and Logan model with arterial sampling, for which the underestimate of V T is negligible, measure V T with high reliability and validity .…”

Transport of Selected PET Radiotracers by Human P-Glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2): An In Vitro Screening

“…Further studies should focus on the brain distribution of befloxatone in the presence of a BCRP inhibitor in vivo. The bias introduced by the BCRP-mediated transport on the brain kinetic parameters of 11 C-befloxatone could be evaluated in baboons and humans using previously described quantification methods (43).…”