Recent developments in TSPO PET imaging as a biomarker of neuroinflammation in neurodegenerative disorders

Eryn L. Werry, Fiona M. Bright, Olivier Piguet, Lars M. Ittner, Glenda M. Halliday, John R. Hodges, Matthew C. Kiernan, Clement T. Loy, Jillian J. Kril, Michael Kassiou*

*Corresponding author for this work

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Neuroinflammation is an inflammatory response in the brain and spinal cord, which can involve the activation of microglia and astrocytes. It is a common feature of many central nervous system disorders, including a range of neurodegenerative disorders. An overlap between activated microglia, pro-inflammatory cytokines and translocator protein (TSPO) ligand binding was shown in early animal studies of neurodegeneration. These findings have been translated in clinical studies, where increases in TSPO positron emission tomography (PET) signal occur in disease-relevant areas across a broad spectrum of neurodegenerative diseases. While this supports the use of TSPO PET as a biomarker to monitor response in clinical trials of novel neurodegenerative therapeutics, the clinical utility of current TSPO PET radioligands has been hampered by the lack of high affinity binding to a prevalent form of polymorphic TSPO (A147T) compared to wild type TSPO. This review details recent developments in exploration of ligand-sensitivity to A147T TSPO that have yielded ligands with improved clinical utility. In addition to developing a non-discriminating TSPO ligand, the final frontier of TSPO biomarker research requires developing an understanding of the cellular and functional interpretation of the TSPO PET signal. Recent insights resulting from single cell analysis of microglial phenotypes are reviewed.

Original languageEnglish
Article number3161
Pages (from-to)1-21
Number of pages21
JournalInternational Journal of Molecular Sciences
Volume20
Issue number13
DOIs
Publication statusPublished - 1 Jul 2019

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Astrocytes
  • Microglia
  • Neurodegeneration
  • Neuroinflammation
  • Translocator protein

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