title: 11C-PBR28 and18F-PBR111 Detect White Matter Inflammatory Heterogeneity in Multiple Sclerosis.
abstract: The 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 or18F-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.
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Gourab
authors.initials: G
authors.lastname: Datta
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.|Centre for Affective Disorders, Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Colasanti
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Kalk
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Owen
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Gregory
authors.initials: G
authors.lastname: Scott
authors.affiliation: Imanova Centre for Imaging Sciences, London, United Kingdom.
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.|Imanova Centre for Imaging Sciences, London, United Kingdom.
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Lingford-Hughes
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Omar
authors.initials: O
authors.lastname: Malik
authors.affiliation: Queen Square Multiple Sclerosis Centre, Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Olga
authors.initials: O
authors.lastname: Ciccarelli
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Nicholas
authors.affiliation: Department of Computing, Imperial College London, London, United Kingdom; and.
authors.forename: Lei
authors.initials: L
authors.lastname: Nei
authors.affiliation: Department of Medicine, Surgery and Neurology, University of Siena, Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Battaglini
authors.affiliation: Department of Medicine, Surgery and Neurology, University of Siena, Siena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom p.matthews@imperial.ac.uk.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
mesh_terms: D000328:Adult; D001692:Biological Transport; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: C526315:(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; C550561:2-(6-chloro-2-(4-(3-fluoropropoxy)phenyl)imidazo(1,2-a)pyridin-3-yl)-N,N-diethylacetamide; D008024:Ligands; D011725:Pyridines; D011743:Pyrimidines
keywords: PET; TSPO; microglia; multiple sclerosis; white matter lesions