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浙江大学学报（医学版）
浙江大学学报（医学版）  2021, Vol. 50 Issue (5): 666-673    DOI: 10.3724/zdxbyxb-2021-0063
综述     
大麻素1型受体正电子发射断层显像在神经精神疾病中的应用进展
马丽娟1,吴爽1,张凯2,田梅1,张宏1,3,4,*()
1.浙江大学医学院附属第二医院核医学科 浙江大学医学PET中心 浙江省医学分子影像重点实验室 浙江大学核医学与分子影像研究所，浙江 杭州 310009
2.日本理化学研究所生命机能研究中心健康与病态科学研究室，日本 神户 650-0047
3.浙江大学生物医学工程教育部重点实验室，浙江 杭州 310027
4.浙江大学生物医学工程与仪器科学学院，浙江 杭州 310027
Progress on the application of positron emission tomography imaging of cannabinoid type 1 receptor in neuropsychiatric diseases
MA Lijuan1,WU Shuang1,ZHANG Kai2,TIAN Mei1,ZHANG Hong1,3,4,*()
1. Department of Nuclear Medicine, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University Medical PET Center, Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou 310009, China;
2. Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan;
3. Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou 310027, China;
4. College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027, China
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摘要：

大麻素1型受体（CB1R）作为内源性大麻素系统的主要成员，是中枢神经系统表达最丰富的受体之一。CB1R主要分布在突触前神经元的轴突末梢，参与神经元兴奋性及突触可塑性调节，在多种神经精神疾病的致病机制中发挥着重要作用。近年来CB1R放射性配体的不断研发及正电子发射断层成像（PET）等分子影像技术的日渐成熟，有助于实现CB1R在中枢神经系统中表达与分布的在体可视化。目前，CB1R PET显像可以有效评估亨廷顿病及精神分裂症等神经精神疾病患者体内的CB1R水平变化及其与病情严重程度之间的联系，从而为神经精神疾病诊治提供新的见解。本文就CB1R PET显像在阿尔茨海默病、帕金森病、亨廷顿病、精神分裂症、创伤后应激障碍、大麻使用障碍及抑郁症中的应用进展进行综述。
关键词： 大麻素1型受体;  正电子发射断层成像;  神经退行性变性疾病;  精神疾病;  精神分裂症;  综述    
Abstract:

Cannabinoid type 1 receptor (CB1R), as the major member of the endocannabinoid system, is among the most abundant receptors expressed in the central nervous system. CB1R is mainly located on the axon terminals of presynaptic neurons and participate in the modulation of neuronal excitability and synaptic plasticity, playing an important role in the pathogenesis of various neuropsychiatric diseases. In recent years, the consistent development of CB1R radioligands and the maturity of molecular imaging techniques, particularly positron emission tomography (PET) may help to visualize the expression and distribution of CB1R in central nervous system in vivo. At present, CB1R PET imaging can effectively evaluate the changes of CB1R levels in neuropsychiatric diseases such as Huntington’s disease and schizophrenia, and its correlation with the disease severity, therefore providing new insights for the diagnosis and treatment of neuropsychiatric diseases. This article reviews the application of CB1R PET imaging in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, schizophrenia, post-traumatic stress disorder, cannabis use disorder and depression.
Key words: Cannabinoid type 1 receptor    Positron emission tomography    Neurodegene-rative disease    Mental disease    Schizophrenia    Review
收稿日期: 2021-03-08 出版日期: 2021-12-29
:  R445  
基金资助: 国家自然科学基金（81725009，82030049，32027802）
通讯作者: 张宏     E-mail: hzhang21@zju.edu.cn
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引用本文:

马丽娟,吴爽,张凯,田梅,张宏. 大麻素1型受体正电子发射断层显像在神经精神疾病中的应用进展[J]. 浙江大学学报（医学版）, 2021, 50(5): 666-673.

MA Lijuan,WU Shuang,ZHANG Kai,TIAN Mei,ZHANG Hong. Progress on the application of positron emission tomography imaging of cannabinoid type 1 receptor in neuropsychiatric diseases. J Zhejiang Univ (Med Sci), 2021, 50(5): 666-673.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0063    或    https://www.zjujournals.com/med/CN/Y2021/V50/I5/666

显像剂名称

显像剂

类型

亲和力

Ki值（nmol/L）

脂水分布系数logD值*

脑内主要分布

优点

缺点

在神经精神疾病中摄取情况

11C-OMAR[19-24]

拮抗剂

2.05

3.30

苍白球、扣带回、壳核、海马、小脑、皮层

较强选择性、亲和力及特异性，可逆，洗脱快

脑摄取较少

精神分裂症摄取增加或摄取减少

创伤后应激障碍摄取增加

大麻使用障碍摄取减少

11C-SD5024[20]

拮抗剂

0.47

3.79

额叶、顶叶、颞叶、扣带回、尾状核、小脑

强特异性，中等亲和力及脑摄取

洗脱较慢

—

18F-MK-9470[20，25-31]

反向激动剂

0.10

4.70

皮层、海马、尾状核、壳核、小脑

较强选择性及脑摄取，强亲和力，中度特异性，稳定

洗脱较慢

阿尔茨海默病摄取未见差异

帕金森病摄取减少

亨廷顿病摄取减少

精神分裂症摄取增加

大麻使用障碍摄取减少

18F-FMPEP-d2[20，32-35]

反向激动剂

0.11

4.20

前额叶皮层、壳核、海马、小脑

强选择性、脑摄取、亲和力、特异性及稳定性

易脱氟及洗脱较慢

阿尔茨海默病摄取减少

精神分裂症摄取减少

大麻使用障碍摄取减少

11C-MePPEP[20，34，36]

反向激动剂

0.11

4.80

前额叶皮层、枕叶皮层、海马、壳核、丘脑、小脑

强脑摄取、特异性及亲和力，稳定及可逆

洗脱慢

精神分裂症摄取减少

18F-FPATPP[18]

反向激动剂

—

—

顶颞叶皮层、纹状体、额叶皮层、海马、小脑

强选择性、特异性及稳定性，低脱氟，洗脱快

合成复杂

—
表 1  第二代大麻素1型受体正电子发射断层成像显像剂特点及临床应用
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