11C-harmine as a tracer for monoamine oxidase A (MAO-A): in vitro and in vivo studies.
Frozen-section autoradiography in rat brain sections as well as in vivo positron emission tomography (PET) studies in monkey brain were used for the determination of binding characteristics of O-[methyl-11C]harmine in an attempt to validate this ligand for the assessment of monoamine oxidase A (MAO-A). In frozen sections, the binding of [11C]harmine showed an apparent KD of the binding of 2 nM. The specific binding was inhibited by nanomolar concentrations of clorgyline, esuprone, brofaromine, and Ro 41-1049. The in vivo kinetic pattern in the monkey brain indicated a significant trapping, which was inhibited by pretreatment with clorgyline, moclobemide, or harmine. Different approaches for a quantitative determination of MAO-A enzyme binding were attempted and demonstrated an IC50 dose of harmine in the range of 0.05-0.1 mg/kg. The studies give strong indications for the validity of [11C]harmine as an in vivo tracer for the assessment of MAO-A enzyme binding in the brain.
Bergström
M
M
Subfemtomole Biorecognition Project, Uppsala University, Sweden.
Westerberg
G
G
Långström
B
B
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000201:enzymology*; D006247:Harmine / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014055:Tomography, Emission-Computed
D006247:Harmine; D008995:Monoamine Oxidase