RT Journal Article SR Electronic T1 In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with 18F-PBR111 PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1112 OP 1118 DO 10.2967/jnumed.113.135129 VO 55 IS 7 A1 Alessandro Colasanti A1 Qi Guo A1 Nils Muhlert A1 Paolo Giannetti A1 Mayca Onega A1 Rexford D. Newbould A1 Olga Ciccarelli A1 Stuart Rison A1 Charlotte Thomas A1 Richard Nicholas A1 Paolo A. Muraro A1 Omar Malik A1 David R. Owen A1 Paola Piccini A1 Roger N. Gunn A1 Eugenii A. Rabiner A1 Paul M. Matthews YR 2014 UL http://jnm.snmjournals.org/content/55/7/1112.abstract AB 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 ρ = 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.