Glial Activity Load on PET Reveals Persistent "Smoldering" Inflammation in MS Despite Disease-Modifying Treatment: 18 F-PBR06 Study.

Autor:	Singhal T, Cicero S; From the Department of Neurology, PET Imaging Program in Neurologic Diseases., Rissanen E; From the Department of Neurology, PET Imaging Program in Neurologic Diseases., Ficke J; From the Department of Neurology, PET Imaging Program in Neurologic Diseases., Kukreja P; From the Department of Neurology, PET Imaging Program in Neurologic Diseases., Vaquerano S; From the Department of Neurology, PET Imaging Program in Neurologic Diseases., Glanz B; Department of Neurology, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases., Dubey S; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology., Sticka W; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology., Seaver K; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology., Kijewski M; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology., Callen AM; Department of Neurology, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases., Chu R; Department of Neurology, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases., Carter K; From the Department of Neurology, PET Imaging Program in Neurologic Diseases., Silbersweig D; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Chitnis T; Department of Neurology, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases., Bakshi R; Department of Neurology, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases., Weiner HL; Department of Neurology, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases.
Jazyk:	angličtina
Zdroj:	Clinical nuclear medicine [Clin Nucl Med] 2024 Jun 01; Vol. 49 (6), pp. 491-499. Date of Electronic Publication: 2024 Apr 17.
DOI:	10.1097/RLU.0000000000005201
Abstrakt:	Purpose of the Report: 18 F-PBR06-PET targeting 18-kDa translocator protein can detect abnormal microglial activation (MA) in multiple sclerosis (MS). The objectives of this study are to develop individualized mapping of MA using 18 F-PBR06, to determine the effect of disease-modifying treatment (DMT) efficacy on reducing MA, and to determine its clinical, radiological, and serological correlates in MS patients. Patients and Methods: Thirty 18 F-PBR06-PET scans were performed in 22 MS patients (mean age, 46 ± 13 years; 16 females) and 8 healthy controls (HCs). Logarithmically transformed "glial activity load on PET" scores (calculated as the sum of voxel-by-voxel z -scores ≥4), "lnGALP," were compared between MS and HC and between MS subjects on high-efficacy DMTs (H-DMT, n = 13) and those on no or lower-efficacy treatment, and correlated with clinical measures, serum biomarkers, and cortical thickness. Results: Cortical gray matter (CoGM) and white matter (WM) lnGALP scores were higher in MS versus HC (+33% and +48%, P < 0.001). In H-DMT group, CoGM and WM lnGALP scores were significantly lower than lower-efficacy treatment ( P < 0.01) but remained abnormally higher than in HC group ( P = 0.006). Within H-DMT patients, CoGM lnGALP scores correlated positively with physical disability, fatigue and serum glial fibrillary acid protein levels ( r = 0.65-0.79, all P 's < 0.05), and inversely with cortical thickness ( r = -0.66, P < 0.05). Conclusions: High-efficacy DMTs decrease, but do not normalize, CoGM and WM MA in MS patients. Such "residual" MA in CoGM is associated with clinical disability, serum biomarkers, and cortical degeneration. Individualized mapping of translocator protein PET using 18 F-PBR06 is clinically feasible and can potentially serve as an imaging biomarker for evaluating "smoldering" inflammation in MS patients. Competing Interests: Conflicts of interest and sources of funding: T.S. has received research support from Novartis Pharmaceuticals and Genzyme-Sanofi; consulting fees from Novartis Pharmaceuticals, Genentech, EMD Serono, Genzyme-Sanofi, and TG Therapeutics; speaking fees from Tiziana Life Sciences; and research funding from Nancy Davis Foundation's “Race to Erase MS” program, Ann Romney Center for Neurologic Diseases, Harvard Neuro-Discovery Center, National Multiple Sclerosis Society, Department of Defense, and Water Cove Charitable Foundation. E.R. has received a fellowship grant from the Sigrid Juselius Foundation and research grant from the Sakari Alhopuro Foundation. T.C. has received compensation for consulting from Biogen, Novartis Pharmaceuticals, Roche Genentech, and Sanofi Genzyme, and has received research support from the National Institutes of Health, National MS Society, US Department of Defense, Sumaira Foundation, Brainstorm Cell Therapeutics, EMD Serono, I-MAB Biopharma, Mallinckrodt ARD, Novartis Pharmaceuticals, Octave Bioscience, Roche Genentech, and Tiziana Life Sciences. R.B. has received consulting fees from Bristol-Myers Squibb and EMD Serono, and research support from Bristol-Myers Squibb, EMD Serono, and Novartis. H.L.W. has received research support from Cure Alzheimer's Fund, EMD Serono Inc, Genentech Inc, National Institutes of Health, National Multiple Sclerosis Society, Sanofi Genzyme, and Verily Life Sciences, and has received payment for consulting from Genentech, Inc, IM Therapeutics, I-MAB Biopharma, MedDay Pharmaceuticals, Tiziana Life Sciences, and vTv Therapeutics. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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