Turku PET Centre (M.S., J.T., M.M., A.V., S.S., J.K., J. Rokka, M.N., J. Rinne, E.R., L.A.), Turku University Hospital and University of Turku; Division of Clinical Neurosciences (M.S., M.N., J. Rinne, E.R., L.A.), Turku University Hospital and University of Turku; and Department of Radiology (R.P.), University Hospital and University of Turku, Finland.
Neurol Neuroimmunol Neuroinflamm. 2019 Jun 7;6(4):e574. doi: 10.1212/NXI.0000000000000574. eCollection 2019 Jul.
To evaluate whether natalizumab treatment reduces microglial activation in MS.
We measured microglial activation using the 18-kDa translocator protein (TSPO)-binding radioligand [C]PK11195 and PET imaging in 10 patients with MS before and after 1 year treatment with natalizumab. Microglial activation was evaluated as the distribution volume ratio (DVR) of the specifically bound radioligand in brain white and gray matter regions of interest. MRI and disability measurements were performed for comparison. Evaluation was performed identically with 11 age- and sex-matched patients with MS who had no MS therapy.
Natalizumab treatment reduced microglial activation in the normal-appearing white matter (NAWM; baseline DVR vs DVR after 1 year of treatment 1.25 vs 1.22, = 0.014, Wilcoxon) and at the rim of chronic lesions (baseline DVR vs DVR after 1 year of treatment 1.24 vs 1.18, = 0.014). In patients with MS with no treatment, there was an increase in microglial activation at the rim of chronic lesions (1.23 vs 1.27, = 0.045). No alteration was observed in microglial activation in gray matter areas. In the untreated patient group, higher microglial activation at baseline was associated with more rapid disability progression during an average of 4 years of follow-up.
TSPO-PET imaging can be used as a tool to assess longitudinal changes in microglial activation in the NAWM and in the perilesional areas in the MS brain in vivo. Natalizumab treatment reduces the diffuse compartmentalized CNS inflammation related to brain resident innate immune cells.
评估那他珠单抗治疗是否能减少多发性硬化症中的小胶质细胞激活。
我们使用 18kDa 转位蛋白（TSPO）结合放射性配体[C]PK11195 和 PET 成像，在 10 名接受那他珠单抗治疗 1 年后的多发性硬化症患者和 11 名未接受多发性硬化症治疗的年龄和性别匹配的多发性硬化症患者中，测量小胶质细胞的激活情况。通过大脑白质和灰质感兴趣区中特异性结合放射性配体的分布容积比（DVR）来评估小胶质细胞的激活。同时进行 MRI 和残疾测量以进行比较。使用相同的方法对两组患者进行评估。
那他珠单抗治疗降低了正常外观白质（NAWM；基线 DVR 与治疗 1 年后的 DVR，1.25 比 1.22， = 0.014，Wilcoxon）和慢性病变边缘的小胶质细胞激活（基线 DVR 与治疗 1 年后的 DVR，1.24 比 1.18， = 0.014）。在未接受治疗的多发性硬化症患者中，慢性病变边缘的小胶质细胞激活增加（1.23 比 1.27， = 0.045）。在灰质区域未观察到小胶质细胞激活的变化。在未治疗的患者组中，基线时更高的小胶质细胞激活与平均 4 年随访期间更快的残疾进展相关。
TSPO-PET 成像可作为一种工具，用于评估多发性硬化症患者大脑中 NAWM 和病变周围区域小胶质细胞激活的纵向变化。那他珠单抗治疗减少了与脑固有免疫细胞相关的弥漫性中枢神经系统炎症。
