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In Vivo assessment of brain white matter inflammation in multiple sclerosis with (18)F-PBR111 PET

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posted on 2023-06-07, 06:33 authored by Alessandro ColasantiAlessandro Colasanti, Qi Guo, Nils Muhlert, Paolo Giannetti, Mayca Onega, Rexford D Newbould, Olga Ciccarelli, Stuart Rison, Charlotte Thomas, Richard Nicholas, Paolo A Muraro, Omar Malik, David R Owen, Paolo Piccini, Roger N Gunn, Eugenii A Rabiner, Paul M Matthews
PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used 18F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. Methods: 18F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. Results: 18F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P < 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher 18F-PBR111 binding in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white matter with reduced MTR (P < 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean 18F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ? = 0.62, P < 0.05). Conclusion: This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune response in MS for differentiation of antiinflammatory effects of new medicines and their longer term impact on clinical outcome.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Journal of Nuclear Medicine

ISSN

0161-5505

Publisher

Society of Nuclear Medicine

Issue

7

Volume

55

Page range

1112-1118

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-05-31

First Open Access (FOA) Date

2019-06-04

First Compliant Deposit (FCD) Date

2019-05-31

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