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Cited by 111Neuroinflammation and Neurodegeneration MechanismsMedical Imaging Techniques and ApplicationsPharmacological Receptor Mechanisms and Effects

Sifting through the surfeit of neuroinflammation tracers

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Cumming, Paul, Burgher, Bjorn, Patkar, Omkar, Breakspear, Michael, Vasdev, Neil, Thomas, Paul, Liu, Guo-Jun, Banati, Richard·2018·Journal of Cerebral Blood Flow & Metabolism
DOI 10.1177/0271678x17748786PMC PMC5951023
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Abstract

The first phase of molecular brain imaging of microglial activation in neuroinflammatory conditions began some 20 years ago with the introduction of [ 11 C]-( R)-PK11195, the prototype isoquinoline ligand for translocator protein (18 kDa) (TSPO). Investigations by positron emission tomography (PET) revealed microgliosis in numerous brain diseases, despite the rather low specific binding signal imparted by [ 11 C]-( R)-PK11195. There has since been enormous expansion of the repertoire of TSPO tracers, many with higher specific binding, albeit complicated by allelic dependence of the affinity. However, the specificity of TSPO PET for revealing microglial activation not been fully established, and it has been difficult to judge the relative merits of the competing tracers and analysis methods with respect to their sensitivity for detecting microglial activation. We therefore present a systematic comparison of 13 TSPO PET and single photon computed tomography (SPECT) tracers belonging to five structural classes, each of which has been investigated by compartmental analysis in healthy human brain relative to a metabolite-corrected arterial input. We emphasize the need to establish the non-displaceable binding component for each ligand and conclude with five recommendations for a standard approach to define the cellular distribution of TSPO signals, and to characterize the properties of candidate TSPO tracers.

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  • [11C]PK11195 is a TSPO PET tracer still routinely used in clinical imaging but has a poor signal-to-noise ratio due to low binding affinity.

    “One of the earliest TSPO PET tracers is [11C]PK11195, still routinely used in clinical imaging but hampered by the poor signal-to-noise ratio arising from its low binding affinity [16, 17].”

    From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [17]

    The Introduction identifies [11C]-(R)-PK11195 as a prototype TSPO PET tracer used in patients and reports its low specific imaging signal. It does not attribute that signal specifically to low binding affinity; instead, it suggests low brain free fraction and/or competition from endogenous ligands. The Conclusions also say [11C]-labelled tracers are not widely available for routine use, so routine clinical use is not established here. Page numbers are unavailable in our copy. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Cumming, P., Burgher, B., Patkar, O., Breakspear, M., Vasdev, N., Thomas, P., Liu, G.-J., & Banati, R.
Affiliations
  • Queensland University of Technology (AU)
  • QIMR Berghofer Medical Research Institute (AU)
  • Harvard University (US)
  • The University of Queensland (AU)
  • The University of Sydney (AU)
Corresponding author
Cumming, Paul
ORCID
Venue
Journal of Cerebral Blood Flow & Metabolism
Publisher
SAGE Publications
Published
2017-12-19
Volume
38
Issue
2
Pages
204-224
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
DOI
10.1177/0271678x17748786
PMC
PMC5951023
OpenAlex
W2779020741
Cited by
111
References
0
Citations by year
2026: 1 · 2025: 7 · 2024: 9 · 2023: 14 · 2022: 13 · 2021: 29 · 2020: 17 · 2019: 13 · 2018: 8
FWCI
1.00
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
Keywords
translocator protein (TSPO), microglial activation, neuroinflammation, [11C]PK11195, SPECT radiotracer, compartmental analysis
MeSH terms
Humans, Inflammation, Nervous System Diseases, Biomarkers, Tomography, Emission-Computed, Single-Photon, Microglia, Positron-Emission Tomography

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