From the Department of Neurology, PET Imaging Program in Neurologic Diseases.
Department of Neurology, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases.
Clin Nucl Med. 2024 Jun 1;49(6):491-499. doi: 10.1097/RLU.0000000000005201. Epub 2024 Apr 17.
18 F-PBR06-PET targeting 18-kDa translocator protein can detect abnormal microglial activation (MA) in multiple sclerosis (MS). The objectives of this study are to develop individualized mapping of MA using 18 F-PBR06, to determine the effect of disease-modifying treatment (DMT) efficacy on reducing MA, and to determine its clinical, radiological, and serological correlates in MS patients.
Thirty 18 F-PBR06-PET scans were performed in 22 MS patients (mean age, 46 ± 13 years; 16 females) and 8 healthy controls (HCs). Logarithmically transformed "glial activity load on PET" scores (calculated as the sum of voxel-by-voxel z -scores ≥4), "lnGALP," were compared between MS and HC and between MS subjects on high-efficacy DMTs (H-DMT, n = 13) and those on no or lower-efficacy treatment, and correlated with clinical measures, serum biomarkers, and cortical thickness.
Cortical gray matter (CoGM) and white matter (WM) lnGALP scores were higher in MS versus HC (+33% and +48%, P < 0.001). In H-DMT group, CoGM and WM lnGALP scores were significantly lower than lower-efficacy treatment ( P < 0.01) but remained abnormally higher than in HC group ( P = 0.006). Within H-DMT patients, CoGM lnGALP scores correlated positively with physical disability, fatigue and serum glial fibrillary acid protein levels ( r = 0.65-0.79, all P 's < 0.05), and inversely with cortical thickness ( r = -0.66, P < 0.05).
High-efficacy DMTs decrease, but do not normalize, CoGM and WM MA in MS patients. Such "residual" MA in CoGM is associated with clinical disability, serum biomarkers, and cortical degeneration. Individualized mapping of translocator protein PET using 18 F-PBR06 is clinically feasible and can potentially serve as an imaging biomarker for evaluating "smoldering" inflammation in MS patients.
18 kDa 转位蛋白的 18 F-PBR06-PET 可检测多发性硬化症（MS）中的异常小胶质细胞激活（MA）。本研究的目的是使用 18 F-PBR06 对 MA 进行个体化成像，确定疾病修正治疗（DMT）对降低 MA 的效果，并确定其在 MS 患者中的临床、放射学和血清学相关性。
对 22 例 MS 患者（平均年龄 46±13 岁，16 名女性）和 8 名健康对照（HC）进行了 30 次 18 F-PBR06-PET 扫描。比较 MS 和 HC 之间以及高效 DMT（H-DMT，n=13）和低效或无治疗组之间 MS 患者之间的对数转换“PET 上的神经胶质活性负荷”评分（计算为≥4 的体素 z 分数总和）“lnGALP”。并与临床指标、血清生物标志物和皮质厚度相关。
MS 患者的皮质灰质（CoGM）和白质（WM）lnGALP 评分高于 HC（分别增加 33%和 48%，P<0.001）。在 H-DMT 组，CoGM 和 WM 的 lnGALP 评分明显低于低疗效治疗组（P<0.01），但仍高于 HC 组（P=0.006）。在 H-DMT 患者中，CoGM 的 lnGALP 评分与躯体残疾、疲劳和血清神经胶质纤维酸性蛋白水平呈正相关（r=0.65-0.79，所有 P'<0.05），与皮质厚度呈负相关（r=-0.66，P'<0.05）。
高效 DMT 可降低 MS 患者的 CoGM 和 WM MA，但不能使其正常化。CoGM 中这种“残留”的 MA 与临床残疾、血清生物标志物和皮质退变有关。使用 18 F-PBR06 进行转位蛋白 PET 的个体化成像在临床上是可行的，可能可作为评估 MS 患者“潜伏”炎症的影像学生物标志物。
