PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain.
PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain.
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活体人脑区域乙酰胆碱浓度变化的 PET 成像估计。
DOI：
10.1093/cercor/bhaa387
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Hillmer,AnselT
中科院分区：
文献类型：
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作者：
Smart,Kelly;Naganawa,Mika;Baldassarri,StephenR;Nabulsi,Nabeel;Ropchan,Jim;Najafzadeh,Soheila;Gao,Hong;Navarro,Antonio;Barth,Vanessa;Esterlis,Irina;Cosgrove,KellyP;Huang,Yiyun;Carson,RichardE;Hillmer,AnselT
乙酰胆碱（ACh）在纹状体和皮层中具有不同的功能，两者之间的失衡可能导致神经精神疾病。临床前研究表明，纹状体中的ACh浓度明显较高。这项工作的目的是利用正电子发射断层扫描（PET）成像估计药物占用胆碱能受体，探索ACh在整个人脑的变化，因为这些措施可以通过竞争与内源性神经递质的影响。分析了健康人类志愿者（n= 4）和非人灵长类动物（n= 2）在存在毒蕈碱拮抗剂东莨菪碱的情况下使用M1选择性放射性示踪剂[11 C] LSN 3172176扫描的PET扫描，以及人类志愿者（n= 10）在尼古丁激发期间使用α4β2* 烟碱配体（−）-[18 F]氟巴汀扫描的PET扫描。在所有情况下，纹状体区域内的占用估计值始终较低（M1/东莨菪碱人扫描，纹状体中占有率为31 ± 3.4%，纹状体外区域中占有率为43 ± 2.9%，p= 0.0094;非人灵长类扫描，42 ± 26%对69 ± 28%，p < 0.0001; α4β2*/尼古丁扫描，67 ± 15% vs. 74 ± 16%，p = 0.0065），表明纹状体ACh浓度较高。受试者水平的措施，这些浓度差异进行了估计，并产生区域乙酰胆碱浓度梯度的全脑图像。这些结果构成了第一次在活体脑中的ACh浓度的区域变化的体内估计，并提供了一种新的实验方法来评估潜在的ACh失衡的临床人群。
Acetylcholine (ACh) has distinct functional roles in striatum compared with cortex, and imbalance between these systems may contribute to neuropsychiatric disease. Preclinical studies indicate markedly higher ACh concentrations in the striatum. The goal of this work was to leverage positron emission tomography (PET) imaging estimates of drug occupancy at cholinergic receptors to explore ACh variation across the human brain, because these measures can be influenced by competition with endogenous neurotransmitter. PET scans were analyzed from healthy human volunteers (n= 4) and nonhuman primates (n= 2) scanned with the M1-selective radiotracer [11C]LSN3172176 in the presence of muscarinic antagonist scopolamine, and human volunteers (n= 10) scanned with the α4β2*nicotinic ligand (−)-[18F]flubatine during nicotine challenge. In all cases, occupancy estimates within striatal regions were consistently lower (M1/scopolamine human scans, 31 ± 3.4% occupancy in striatum, 43 ± 2.9% in extrastriatal regions,p= 0.0094; nonhuman primate scans, 42 ± 26% vs. 69 ± 28%,p< 0.0001; α4β2*/nicotine scans, 67 ± 15% vs. 74 ± 16%,p= 0.0065), indicating higher striatal ACh concentration. Subject-level measures of these concentration differences were estimated, and whole-brain images of regional ACh concentration gradients were generated. These results constitute the first in vivo estimates of regional variation in ACh concentration in the living brain and offer a novel experimental method to assess potential ACh imbalances in clinical populations.