Altmetric

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

File Description SizeFormat 
Gourab_JNUMED-2017-GD_REVISEDFINALACCEPTED.pdfAccepted version605.88 kBAdobe PDFView/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:Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx