MAPPING HUMAN-BRAIN MONOAMINE OXIDASE-A AND OXIDASE-B WITH C-11 LABELED SUICIDE INACTIVATORS AND PET
MAPPING HUMAN-BRAIN MONOAMINE OXIDASE-A AND OXIDASE-B WITH C-11 LABELED SUICIDE INACTIVATORS AND PET
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DOI：
10.1126/science.3099392
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发表时间：
1987-01-23
期刊：
影响因子：
56.9
通讯作者：
LANGSTROM, B
中科院分区：
文献类型：
--
作者：
FOWLER, JS;MACGREGOR, RR;LANGSTROM, B
用~(11)C标记的自杀酶灭活剂、氯吉林和L-丙戊烯静脉注射和正电子发射断层扫描，在活体人脑内观察到单胺氧化酶(MAO)A和B型的分布。大脑对这两种11C示踪剂的快速摄取和放射性滞留表明存在不可逆转的陷阱。11C的解剖分布与尸检资料中MAO A和MAO B在人脑中的分布基本一致。纹状体、丘脑和脑干含有较高的MAO活性。一名受试者服用MAO抑制剂苯乙肼后，[11C]Clorygyline和L-[11C]异丙烯基的摄取幅度均显著降低。11C标记的非活性(D-)和活性(L-)对映体的脑摄取和保留的比较表明，非活性对映体迅速清除，活性对映体保留在富含MAO B的脑结构中，这与已知的MAO B对L-丙戊烯对映体的立体选择性一致。预先使用未标记的L-丙戊烯可阻止L-[11C]丙戊烯的保留。因此，用正电子发射体标记的自杀性酶失活剂可以用来定量MAO在人脑结构中的分布和动力学特征。
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]clorygyline 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.