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[(11)C]PBR28 or [(18)F]PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis
File | Description | Size | Format | |
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Gourab_JNUMED-2017-GD_REVISEDFINALACCEPTED.pdf | Accepted version | 605.88 kB | Adobe PDF | View/Open |
Title: | [(11)C]PBR28 or [(18)F]PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis |
Authors: | Datta, G Colasanti, A Kalk, N Owen, DR Scott, G Rabiner, EI Gunn, R Lingford-Hughes, A Malik, O Ciccarelli, O Nicholas, R Nie, L Battaglini, M De Stefano, N Matthews, P |
Item Type: | Journal Article |
Abstract: | Objective: To assess microglial activation in lesions and in normal appearing white matter of multiple sclerosis (MS) patients using positron emission tomography (PET). Methods: 34 MS patients (7 with secondary progressive MS (SPMS), 27 with relapsing remitting MS (RRMS)) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO), binding status underwent PET scanning with TSPO radioligands ((11)C-PBR28 or (18)F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudo-reference region). White matter lesions (WML) were classified as "active" (DVR highest in the lesion), "peripherally active" (peri-lesional DVR highest), "inactive" (DVR highest in surrounding normal appearing white matter, NAWM) or "undifferentiated" (similar DVR across lesion, peri-lesional and NAWM volumes). Results: The mean DVR in NAWM of patients was greater than that of the healthy volunteer white matter for both radioligands. Uptake for individual WML in patients was heterogeneous, but the median WML DVR and NAWM DVR for individual patients were strongly correlated (ρ = 0.94, P = 4x10-11). A higher proportion of lesions were inactive in patients with SPMS (35 %) than RRMS (23 %), but active lesions were found in all patients, including those on highly efficacious treatments. Conclusion: TSPO radioligand uptake was increased in brains of MS patients relative to healthy controls with two TSPO radiotracers. WML showed heterogeneous patterns of uptake. Active lesions were found in patients with both RRMS and SPMS. Their independent prognostic significance needs further investigation. |
Issue Date: | 1-Sep-2017 |
Date of Acceptance: | 1-Mar-2017 |
URI: | http://hdl.handle.net/10044/1/72466 |
DOI: | 10.2967/jnumed.116.187161 |
ISSN: | 1535-5667 |
Publisher: | Society of Nuclear Medicine |
Start Page: | 1477 |
End Page: | 1482 |
Journal / Book Title: | Journal of Nuclear Medicine |
Volume: | 58 |
Issue: | 9 |
Sponsor/Funder: | Medical Research Council (MRC) Medical Research Council (MRC) Medical Research Council (MRC) Medical Research Council (MRC) |
Funder's Grant Number: | MR/N008219/1 MR/N026934/1 G0900897 MR/K501013/1 |
Keywords: | Science & Technology Life Sciences & Biomedicine Radiology, Nuclear Medicine & Medical Imaging multiple sclerosis white matter lesions TSPO PET microglia POSITRON-EMISSION-TOMOGRAPHY IN-VIVO BINDING TRANSLOCATOR PROTEIN DISEASE-ACTIVITY TSPO PET BRAIN MICROGLIA DEMYELINATION NEUROINFLAMMATION PATHOGENESIS PET TSPO microglia multiple sclerosis white matter lesions Adult Biological Transport Brain Female Humans Inflammation Ligands Male Middle Aged Multiple Sclerosis Positron-Emission Tomography Pyridines Pyrimidines White Matter Brain Humans Multiple Sclerosis Inflammation Pyridines Pyrimidines Ligands Positron-Emission Tomography Biological Transport Adult Middle Aged Female Male White Matter Molecular Imaging Neurology PET TSPO microglia multiple sclerosis white matter lesions 1103 Clinical Sciences Nuclear Medicine & Medical Imaging |
Publication Status: | Published |
Conference Place: | United States |
Online Publication Date: | 2017-03-16 |
Appears in Collections: | Department of Brain Sciences |