title: Translocator protein PET imaging for glial activation in multiple sclerosis.
abstract: Glial activation in the setting of central nervous system inflammation is a key feature of the multiple sclerosis (MS) pathology. Monitoring glial activation in subjects with MS, therefore, has the potential to be informative with respect to disease activity. The translocator protein 18 kDa (TSPO) is a promising biomarker of glial activation that can be imaged by positron emission tomography (PET). To characterize the in vivo TSPO expression in MS, we analyzed brain PET scans in subjects with MS and healthy volunteers in an observational study using [(11)C]PBR28, a newly developed translocator protein-specific radioligand. The [(11)C]PBR28 PET showed altered compartmental distribution of TSPO in the MS brain compared to healthy volunteers (p = 0.019). Focal increases in [(11)C]PBR28 binding corresponded to areas of active inflammation as evidenced by significantly greater binding in regions of gadolinium contrast enhancement compared to contralateral normal-appearing white matter (p = 0.0039). Furthermore, increase in [(11)C]PBR28 binding preceded the appearance of contrast enhancement on magnetic resonance imaging in some lesions, suggesting a role for early glial activation in MS lesion formation. Global [(11)C]PBR28 binding showed correlation with disease duration (p = 0.041), but not with measures of clinical disability. These results further define TSPO as an informative marker of glial activation in MS.
authors.affiliation: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Bldg 10 Rm 5C103, Bethesda, MD 20892, USA.
authors.forename: Unsong
authors.initials: U
authors.lastname: Oh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: Vasiliki N
authors.initials: VN
authors.lastname: Ikonomidou
authors.forename: Iordanis E
authors.initials: IE
authors.lastname: Evangelou
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.forename: Erin
authors.initials: E
authors.lastname: Harberts
authors.forename: Yota
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Richert
authors.forename: Joan
authors.initials: J
authors.lastname: Ohayon
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sami S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
mesh_terms: D000081:Acetamides; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology*; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA / Q000096:biosynthesis*
chemical_list: D000081:Acetamides; D015415:Biomarkers; D002250:Carbon Radioisotopes; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human