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Review
. 2021 Jan 14;64(1):123-149.
doi: 10.1021/acs.jmedchem.0c01459. Epub 2020 Dec 30.

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

Lu Hou  1 , Jian Rong  2 , Achi Haider  2 , Daisuke Ogasawara  3 , Cassis Varlow  4 , Michael A Schafroth  3 , Linjing Mu  5 , Jiefeng Gan  1 , Hao Xu  1 , Christopher J Fowler  6 , Ming-Rong Zhang  7 , Neil Vasdev  2   4 , Simon Ametamey  5 , Benjamin F Cravatt  3 , Lu Wang  1   2 , Steven H Liang  2
Affiliations
Review

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

Lu Hou et al. J Med Chem. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Representative chemical structures for CB1R-specific PET tracers
Figure 2.
Figure 2.
Representative chemical structures for CB2R-specific PET tracers
Figure 3.
Figure 3.
Representative chemical structures for FAAH-specific PET tracers
Figure 4.
Figure 4.
Representative chemical structures of MAGL-specific PET tracers
Scheme 1.
Scheme 1.
A general model for the ECS signaling in the nervous system
Scheme 2.
Scheme 2.
Pharmacological properties of FAAH and MALG inhibitors
See this image and copyright information in PMC

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