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 F-FEBMP, a relatively novel TSPO radioligand developed for human studies based on its insensitivity to a common polymorphism, with C-PK11195, as well as other commonly used TSPO radioligands including C-PBR28, C-Ac5216 and F-FEDAA1106. TSPO in cerebral vessels of normal mice was found to provide a major binding site for C-PK11195, C-PBR28 and F-FEDAA1106, in contrast to no overt specific binding of F-FEBMP and C-Ac5216 to this vascular component. In addition, F-FEBMP yielded PET images of microglial TSPO with a higher contrast than C-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 F-FEBMP but not C-PK11195. Our findings support the potential advantage of comparatively glial TSPO-selective radioligands such as F-FEBMP for PET imaging of inflammatory glial cells.