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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Neuroinflammatory Diseases / diagnostic imaging*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / chemistry*
  • Receptors, GABA / chemistry*
  • Small Molecule Libraries / chemistry*


  • Radiopharmaceuticals
  • Receptors, GABA
  • Small Molecule Libraries
  • TSPO protein, human