RT Journal Article
SR Electronic
T1 11C-PBR28 and 18F-PBR111 Detect White Matter Inflammatory Heterogeneity in Multiple Sclerosis
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1477
OP 1482
DO 10.2967/jnumed.116.187161
VO 58
IS 9
A1 Gourab Datta
A1 Alessandro Colasanti
A1 Nicola Kalk
A1 David Owen
A1 Gregory Scott
A1 Eugenii A. Rabiner
A1 Roger N. Gunn
A1 Anne Lingford-Hughes
A1 Omar Malik
A1 Olga Ciccarelli
A1 Richard Nicholas
A1 Lei Nei
A1 Marco Battaglini
A1 Nicola D. Stefano
A1 Paul M. Matthews
YR 2017
UL http://jnm.snmjournals.org/content/58/9/1477.abstract
AB 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 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.