Hou Lu, Rong Jian, Haider Achi, Ogasawara Daisuke, Varlow Cassis, Schafroth Michael A, Mu Linjing, Gan Jiefeng, Xu Hao, Fowler Christopher J, Zhang Ming-Rong, Vasdev Neil, Ametamey Simon, Cravatt Benjamin F, Wang Lu, Liang Steven H
Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, 613 West Huangpu Road, Tianhe District, Guangzhou 510630, China.
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
J Med Chem. 2021 Jan 14;64(1):123-149. doi: 10.1021/acs.jmedchem.0c01459. Epub 2020 Dec 30.
The endocannabinoid system (ECS) is involved in a wide range of biological functions and comprises cannabinoid receptors and enzymes responsible for endocannabinoid synthesis and degradation. Over the past 2 decades, significant advances toward developing drugs and positron emission tomography (PET) tracers targeting different components of the ECS have been made. Herein, we summarized the recent development of PET tracers for imaging cannabinoid receptors 1 (CB1R) and 2 (CB2R) as well as the key enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), particularly focusing on PET neuroimaging applications. State-of-the-art PET tracers for the ECS will be reviewed including their chemical design, pharmacological properties, radiolabeling, as well as preclinical and human PET imaging. In addition, this review addresses the current challenges for ECS PET biomarker development and highlights the important role of PET ligands to study disease pathophysiology as well as to facilitate drug discovery.
内源性大麻素系统(ECS)参与广泛的生物学功能,由大麻素受体以及负责内源性大麻素合成与降解的酶组成。在过去20年里,在开发针对ECS不同组分的药物和正电子发射断层扫描(PET)示踪剂方面取得了重大进展。在此,我们总结了用于成像大麻素受体1(CB1R)和2(CB2R)以及关键酶单酰甘油脂肪酶(MAGL)和脂肪酸酰胺水解酶(FAAH)的PET示踪剂的最新进展,尤其侧重于PET神经成像应用。将对用于ECS的最先进PET示踪剂进行综述,包括其化学设计、药理学特性、放射性标记以及临床前和人体PET成像。此外,本综述探讨了ECS PET生物标志物开发目前面临的挑战,并强调了PET配体在研究疾病病理生理学以及促进药物发现方面的重要作用。
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