Fowler J S, MacGregor R R, Wolf A P, Arnett C D, Dewey S L, Schlyer D, Christman D, Logan J, Smith M, Sachs H
Science. 1987 Jan 23;235(4787):481-5. doi: 10.1126/science.3099392.
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.
通过静脉注射11C标记的自杀性酶灭活剂氯吉兰和L-司来吉兰，并利用正电子发射断层扫描技术，已在活体人脑中确定了单胺氧化酶（MAO）A和B型的区域分布。两种11C示踪剂在脑中的快速摄取和放射性滞留表明存在不可逆捕获。11C的解剖分布与尸检材料中MAO A和MAO B在人脑中的分布平行。纹状体、丘脑和脑干含有高MAO活性。在一名接受抗抑郁药MAO抑制剂苯乙肼治疗的受试者中，[11C]氯吉兰和L-[11C]司来吉兰的摄取量均显著降低。对司来吉兰的11C标记的无活性（D-）和活性（L-）对映体在脑中的摄取和滞留进行比较，结果显示无活性对映体快速清除，活性对映体在富含MAO B的脑结构中滞留，这与MAO B对L-司来吉兰已知的立体选择性一致。用未标记的L-司来吉兰预先处理可阻止L-[11C]司来吉兰的滞留。因此，用正电子发射体标记的自杀性酶灭活剂可用于定量MAO在人脑结构中的分布和动力学特征。
