Emerging TSPO-PET Radiotracers for Imaging Neuroinflammation: A Critical Analysis.

The translocator protein (TSPO) is a biomarker for imaging neuroinflammation via Positron Emission Tomography (PET) across a broad range of CNS conditions. Most clinically used PET ligands targeting TSPO have limitations, including high lipophilicity and off-target binding or poor binding to a mutated TSPO isoform present in up to 30% of the population. Research efforts over the past decade have focused on development of improved TSPO PET radiotracers that overcome these limitations. This review provides a critical analysis of the development and validation of these so-called "third-generation" radiotracers in clinical and preclinical settings. We also offer our perspective on the future directions of TSPO PET imaging, including recommendations for overcoming current challenges and capitalizing on emerging opportunities in molecular imaging for neuroinflammatory diseases.