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.

Keywords

Baboons, Monkeys, Primates, Mammals, In vivo, Positron computed tomography, Dopamine, Amines, Tobacco

Citation

Bottlaender, M., Valette, H., Delforge, J., Saba, W., Guenther, I., Curet, O., George, P., Dollé, F., & Grégoire, M. C. (2010). In vivo quantification of monoamine oxidase A in baboon brain: a PET study using [C-11]befloxatone and the multi-injection approach. Journal of Cerebral Blood Flow & Metabolism, 30(4), 792-800. doi:10.1038/jcbfm.2009.242