Detection of Alzheimer’s disease-related neuroinflammation by a PET ligand selective for glial versus vascular translocator protein

A substantial and constitutive expression of translocator protein (TSPO) in cerebral blood vessels hampers the sensitive detection of neuroinflammation characterized by greatly induced TSPO expression in activated glia. Here, we conducted in vivo positron emission tomography (PET) and in vitro autoradiographic imaging of normal and TSPO-deficient mouse brains to compare the binding properties of ¹⁸F-FEBMP, a relatively novel TSPO radioligand developed for human studies based on its insensitivity to a common polymorphism, with ¹¹C-PK11195, as well as other commonly used TSPO radioligands including ¹¹C-PBR28, ¹¹C-Ac5216 and ¹⁸F-FEDAA1106. TSPO in cerebral vessels of normal mice was found to provide a major binding site for ¹¹C-PK11195, ¹¹C-PBR28 and ¹⁸F-FEDAA1106, in contrast to no overt specific binding of ¹⁸F-FEBMP and ¹¹C-Ac5216 to this vascular component. In addition, ¹⁸F-FEBMP yielded PET images of microglial TSPO with a higher contrast than ¹¹C-PK11195 in a tau transgenic mouse modeling Alzheimer’s disease (AD) and allied neurodegenerative tauopathies. Moreover, TSPO expression examined by immunoblotting was significantly increased in AD brains compared with healthy controls, and was well correlated with the autoradiographic binding of ¹⁸F-FEBMP but not ¹¹C-PK11195. Our findings support the potential advantage of comparatively glial TSPO-selective radioligands such as ¹⁸F-FEBMP for PET imaging of inflammatory glial cells.