PET imaging of neuroinflammation: any credible alternatives to TSPO yet?
Level 5 - mechanism / opinion, no new human data
Systematic scoping review of preclinical and translational radiotracer studies without meta-analysis of clinical trials.
PubMed 38997465 · doi:10.1038/s41380-024-02656-9
What was done
Authors conducted a systematic search and scoping review of PET radioligands developed as non-TSPO alternatives for imaging neuroinflammation. They evaluated candidate tracers across microglial markers (P2Y12R, P2X7R, CSF1R, COX), astrocytic markers (MAO-B, I2BS), and non-specific targets (CB2R, S1PRs) to assess their translational and clinical development status.
What was found
The abstract reports no numerical outcomes or effect sizes. Qualitatively, the astrocytic target MAO-B has advanced the furthest into clinical investigations, while radiotracers for S1P1Rs and CSF1R are entering clinical testing. In contrast, targets including CB2R and P2X7R have underperformed in clinical studies due to poor signal or inability to detect disease-related differences. Developing selective markers for microglial activation remains difficult.
Why it matters
TSPO imaging is hindered by non-specific endothelial binding and mixed cellular expression. Identifying distinct microglial and astrocytic PET targets is critical to accurately monitor cell-specific neuroinflammatory mechanisms in brain disorders.
Limits
The abstract does not disclose the total number of included studies, screening databases, or quantitative imaging metrics (such as binding potential or test-retest reliability). Most non-TSPO targets remain in early translational stages with limited human validation.
Cited by
- context TSPO PET imaging can detect activated microglia in living humans.