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

Abstract

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.

• Authors: Bin Ji, Maiko Ono, Tomoteru Yamasaki, Masayuki Fujinaga, Ming-Rong Zhang, Chie Seki, Ichio Aoki, Seiji Kito, Makoto Sawada, Tetsuya Suhara, Naruhiko Sahara, Makoto Higuchi
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 41 Issue 8 Pg. 2076-2089 (08 2021) ISSN: 1559-7016 [Electronic] United States
• PMID: 33557690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bzrp protein, mouse
• Ligands
• Radiopharmaceuticals
• Receptors, GABA

Topics

• Alzheimer Disease (diagnostic imaging, metabolism, pathology)
• Animals
• Brain (diagnostic imaging, metabolism, pathology)
• Disease Models, Animal
• Hippocampus (metabolism, pathology)
• Humans
• Ligands
• Magnetic Resonance Imaging
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Microglia (cytology, metabolism)
• Positron-Emission Tomography
• Radiopharmaceuticals (administration & dosage, chemistry)
• Receptors, GABA (metabolism)