Sifting through the surfeit of neuroinflammation tracers

The first phase of molecular brain imaging of microglial activation in neuroinflammatory conditions began some 20 years ago with the introduction of [11C]-(R)-PK11195, the prototype isoquinoline ligand for translocator protein (18 kDa) (TSPO). Investigations by positron emission tomography (PET) rev...

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Bibliographic Details
Published in:Journal of Cerebral Blood Flow & Metabolism 2018-02, Vol.38 (2), p.204-224
Main Authors: Cumming, Paul, Burgher, Bjorn, Patkar, Omkar, Breakspear, Michael, Vasdev, Neil, Thomas, Paul, Liu, Guo-Jun, Banati, Richard
Format: Article
Language:English
Subjects:
Biomarkers - analysis
Humans
Inflammation - diagnosis
Inflammation - diagnostic imaging
Inflammation - pathology
Microglia - pathology
Nervous System Diseases - diagnosis
Nervous System Diseases - diagnostic imaging
Nervous System Diseases - metabolism
Positron-Emission Tomography
Review
Tomography, Emission-Computed, Single-Photon
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Summary:The first phase of molecular brain imaging of microglial activation in neuroinflammatory conditions began some 20 years ago with the introduction of [11C]-(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 [11C]-(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.
ISSN:0271-678X
1559-7016
DOI:10.1177/0271678X17748786