Nuclear imaging of neuroinflammation:a comprehensive review of [C-11]PK11195 challengers

Neurodegenerative, inflammatory and neoplastic brain disorders involve neuroinflammatory reactions, and a biomarker of neuroinflammation would be useful for diagnostic, drug development and therapy control of these frequent diseases. In vivo imaging can document the expression of the peripheral benzodiazepine receptor (PBR)/translocator protein 18 kDa (TSPO) that is linked to microglial activation and considered a hallmark of neuroinflammation. The prototype positron emission tomography tracer for PBR, [C-11]PK11195, has shown limitations that until now have slowed the clinical applications of PBR imaging. In recent years, dozens of new PET and SPECT radioligands for the PBR have been radio-labelled, and several have been evaluated in imaging protocols. Here we review the new PBR ligands proposed as challengers of [C-11]PK11195, critically analyze preclinical imaging studies and discuss their potential as neuroinflammation imaging agents.