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Science 23 January 1987:
Vol. 235. no. 4787, pp. 481 - 485
DOI: 10.1126/science.3099392
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Articles

Science, Vol 235, Issue 4787, 481-485
Copyright © 1987 by American Association for the Advancement of Science

articles

Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET

JS Fowler, RR MacGregor, AP Wolf, CD Arnett, SL Dewey, D Schlyer, D Christman, J Logan, M Smith, H Sachs, and al. et

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.


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