Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET.
The regional distributions of monoamine oxidase (MAO) types A and B have been identified in human brain in vivo with intravenously injected 11C-labeled suicide enzyme inactivators, clorgyline and L-deprenyl, and positron emission tomography. The rapid brain uptake and retention of radioactivity for both 11C tracers indicated irreversible trapping. The anatomical distribution of 11C paralleled the distribution of MAO A and MAO B in human brain in autopsy material. The corpus striatum, thalamus, and brainstem contained high MAO activity. The magnitudes of uptake of both [11C]clorgyline and L-[11C]deprenyl were markedly reduced in one subject treated with the antidepressant MAO inhibitor phenelzine. A comparison of the brain uptake and retention of the 11C-labeled inactive (D-) and active (L-) enantiomers of deprenyl showed rapid clearance of the inactive enantiomer and retention of the active enantiomer within MAO B-rich brain structures, in agreement with the known stereoselectivity of MAO B for L-deprenyl. Prior treatment with unlabeled L-deprenyl prevented retention of L-[11C]deprenyl. Thus, suicide enzyme inactivators labeled with positron emitters can be used to quantitate the distribution and kinetic characteristics of MAO in human brain structures.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000201:enzymology*; D001933:Brain Stem / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D003010:Clorgyline; D003342:Corpus Striatum / Q000201:enzymology; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism*; D012642:Selegiline; D013788:Thalamus / Q000201:enzymology; D014055:Tomography, Emission-Computed
D012642:Selegiline; D008995:Monoamine Oxidase; D003010:Clorgyline