title: Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases?
abstract: Neuroinflammation is implicated in the pathogenesis of a wide range of neurologic and neuropsychiatric diseases. For over 20 years, (11)C-PK11195 PET, which aims to image expression of the translocator protein (TSPO) on activated microglia in the brain, has been used in preclinical and clinical research to investigate neuroinflammation in vivo in patients with brain diseases. However, (11)C-PK11195 suffers from two major limitations: its low brain permeability and high nonspecific and plasma binding results in a low signal-to-noise ratio, and the use of (11)C restricts its use to PET research centers and hospitals with an on-site cyclotron. In recent years, there has been a great deal of work into the development of new TSPO-specific PET radiotracers. This work has focused on fluorinated radiotracers, which would enable wider use and improved signal-to-noise ratios. These radiotracers have been utilized in preclinical and clinical studies of several neurologic diseases with varying degrees of success. Unfortunately, the application of these second-generation TSPO radiotracers has revealed additional problems, including a polymorphism that affects TSPO binding. In this review, the developments in TSPO imaging are discussed, and current limitations and suggestions for future directions are explored.
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Royal Parade, Parkville, Victoria, Australia lucy.vivash@mh.org.au.
authors.forename: Lucy
authors.initials: L
authors.lastname: Vivash
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Royal Parade, Parkville, Victoria, Australia.
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
mesh_terms: D006801:Humans; D017628:Microglia / Q000000981:diagnostic imaging*; D057054:Molecular Imaging; D009422:Nervous System Diseases / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D018079:Receptors, GABA / Q000737:chemistry*
chemical_list: D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: 11C-PK11195; TSPO; microglia; neurology; positron emission tomography