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[(11)C]PBR28 or [(18)F]PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis

Datta, G; Colasanti, A; Kalk, N; Owen, DR; Scott, G; Rabiner, EIA; Gunn, R; ... Matthews, P; + view all (2017) [(11)C]PBR28 or [(18)F]PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis. Journal of Nuclear Medicine , 58 (9) pp. 1477-1482. 10.2967/jnumed.116.187161. Green open access

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Abstract

OBJECTIVE: of this study was to assess microglial activation in lesions and in normal-appearing white matter (NAWM) of multiple sclerosis (MS) patients using PET. METHODS Thirty-four 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 (11C-PBR28 or 18F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudoreference region). White matter lesions (WMLs) were classified as “active” (DVR highest in the lesion), “peripherally active” (perilesional DVR highest), “inactive” (DVR highest in surrounding NAWM), or “undifferentiated” (similar DVR across lesion, perilesional 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 = 4 × 10−11). 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 the brains of MS patients relative to healthy controls with 2 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.

Type: Article
Title: [(11)C]PBR28 or [(18)F]PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.2967/jnumed.116.187161
Publisher version: http://dx.doi.org/10.2967/jnumed.116.187161
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Molecular Imaging, Neurology, PET, TSPO, microglia, multiple sclerosis, white matter lesions
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1547324
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