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Review
. 2021 Dec 23;64(24):17656-17689.
doi: 10.1021/acs.jmedchem.1c01571. Epub 2021 Dec 14.

The Repertoire of Small-Molecule PET Probes for Neuroinflammation Imaging: Challenges and Opportunities beyond TSPO

Zhen Chen  1   2 , Achi Haider  1   2 , Jiahui Chen  1 , Zhiwei Xiao  1   2 , Luca Gobbi  3 , Michael Honer  3 , Uwe Grether  3 , Steven E Arnold  4 , Lee Josephson  1   2 , Steven H Liang  1   2
Affiliations
Review

The Repertoire of Small-Molecule PET Probes for Neuroinflammation Imaging: Challenges and Opportunities beyond TSPO

Zhen Chen et al. J Med Chem. .

Abstract

Neuroinflammation is an adaptive response of the central nervous system to diverse potentially injurious stimuli, which is closely associated with neurodegeneration and typically characterized by activation of microglia and astrocytes. As a noninvasive and translational molecular imaging tool, positron emission tomography (PET) could provide a better understanding of neuroinflammation and its role in neurodegenerative diseases. Ligands to translator protein (TSPO), a putative marker of neuroinflammation, have been the most commonly studied in this context, but they suffer from serious limitations. Herein we present a repertoire of different structural chemotypes and novel PET ligand design for classical and emerging neuroinflammatory targets beyond TSPO. We believe that this Perspective will support multidisciplinary collaborations in academic and industrial institutions working on neuroinflammation and facilitate the progress of neuroinflammation PET probe development for clinical use.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Cellular and molecular hallmarks of neuroinflammation.
Figure 2.
Figure 2.
Representative PET probes for COX-1.
Figure 3.
Figure 3.
Representative PET probes for COX-2.
Figure 4.
Figure 4.
A) Representative PET probes for ROS and B) mode of action of [11C]26.
Figure 5.
Figure 5.
Representative PET probes for CB2R.
Figure 6.
Figure 6.
Chemical structures of MAO-B selective PET probes.
Figure 7.
Figure 7.
Chemical structures of metabolic trapping agents for MAO.
Figure 8.
Figure 8.
Representative imaging probes for S1PR1 (67-78) and S1PR2 (78 and 79).
Figure 9.
Figure 9.
Representative PET probes for purinergic receptors (compounds 80-86 for P2X7R, compound 87 for P2Y12R).
Figure 10.
Figure 10.
Representative PET probes for CSF1R.
Figure 11.
Figure 11.
Representative PET probes for RAGE (compounds 93-95), MERTK (compound 96) and sEH (compound 97).
Figure 12.
Figure 12.
Representative PET probes for PDE4B (98), PDE4D (99-102), and PDE7 (103-105)
Figure 13.
Figure 13.
Representative imaging probes for CX3CR1 (compound 106), NLRP3 (compound 107 & 108) and MPO (compound 109 & 110)
Figure 14.
Figure 14.
Representative PET probes for GSK-3.
See this image and copyright information in PMC

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