Positron Emission Tomography Imaging of the Endocannabinoid System: Opportunities and Challenges in Radiotracer Development

• Published in: Journal of medicinal chemistry Vol. 64; no. 1; pp. 123 - 149
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14.01.2021
• Subjects: Amidohydrolases - antagonists & inhibitors; Animals; Biomarkers - metabolism; Brain - diagnostic imaging; Brain - metabolism; Endocannabinoids - metabolism; Enzyme Inhibitors - pharmacology; Humans; Positron-Emission Tomography - methods; Receptors, Cannabinoid - metabolism
• ISSN: 0022-2623; 1520-4804; 1520-4804
• DOI: 10.1021/acs.jmedchem.0c01459

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.