PET Center, Department of Diagnostic Radiology, Yale School of Medicine, 801 Howard Avenue, PO Box 208048, New Haven, CT, 06520-8048, USA,
Eur J Nucl Med Mol Imaging. 2015 Jun;42(7):1081-92. doi: 10.1007/s00259-015-3043-4. Epub 2015 Apr 2.
Activated microglia play a key role in inflammatory demyelinating injury in multiple sclerosis (MS). Microglial activation can be measured in vivo using a positron emission tomography (PET) ligand (11)C-PBR28. We evaluated the test-retest variability (TRV) and lesion detectability of (11)C-PBR28 binding in MS subjects and healthy controls (HCs) with high-resolution PET.
Four clinically and radiologically stable relapsing-remitting MS subjects (age 41 ± 7 years, two men/two women) and four HCs (age 42 ± 8 years, 2 two men/two women), matched for translocator protein genotype [two high- and two medium-affinity binders according to DNA polymorphism (rs6971) in each group], were studied for TRV. Another MS subject (age 41 years, male) with clinical and radiological activity was studied for lesion detectability. Dynamic data were acquired over 120 min after injection of 634 ± 101 MBq (11)C-PBR28. For the TRV study, subjects were scanned twice, on average 1.4 weeks apart. Volume of distribution (V T) derived from multilinear analysis (MA1) modeling (t* = 30 min, using arterial input data) was the main outcome measure.
Mean test V T values (ml cm(-3)) were 3.9 ± 1.4 in the whole brain gray matter (GM), 3.6 ± 1.2 in the whole brain white matter (WM) or normal-appearing white matter (NAWM), and 3.3 ± 0.6 in MS WM lesions; mean retest V T values were 3.7 ± 1.0 in GM, 3.3 ± 0.9 in WM/NAWM, and 3.3 ± 0.7 in MS lesions. Test-retest results showed a mean absolute TRV ranging from 7 to 9 % across GM, WM/NAWM, and MS lesions. High-affinity binders demonstrated 30 % higher V T than medium-affinity binders in GM. Focal (11)C-PBR28 uptake was detected in two enhancing lesions of the active MS patient.
High-resolution (11)C-PBR28 PET can visualize focal areas where microglial activation is known to be present and has good test-retest reproducibility in the human brain. (11)C-PBR28 PET is likely to be valuable for monitoring both MS disease evolution and response to therapeutic strategies that target microglial activation.
激活的小胶质细胞在多发性硬化症（MS）的炎症性脱髓鞘损伤中起关键作用。可以使用正电子发射断层扫描（PET）配体（11）C-PBR28 在体内测量小胶质细胞的激活。我们使用高分辨率 PET 评估了 MS 患者和健康对照者（HC）中（11）C-PBR28 结合的测试 - 再测试变异性（TRV）和病变检测能力。
4 名临床和放射学稳定的复发缓解型 MS 患者（年龄 41±7 岁，2 男/2 女）和 4 名 HC（年龄 42±8 岁，2 男/2 女），根据 DNA 多态性（rs6971）（每组两个高亲和力和两个中亲和力结合物）匹配转位蛋白基因型，进行 TRV 研究。另一名年龄为 41 岁的具有临床和放射学活动性的 MS 患者进行了病变检测能力研究。在注射 634±101MBq（11）C-PBR28 后 120 分钟内采集动态数据。用于 TRV 研究的对象平均相隔 1.4 周进行两次扫描。多线性分析（MA1）建模（t*=30 分钟，使用动脉输入数据）得出的分布容积（V T）是主要的观察指标。
整个大脑灰质（GM）的平均测试 V T 值（ml cm（-3））为 3.9±1.4，整个大脑白质（WM）或正常出现的白质（NAWM）为 3.6±1.2，MS WM 病变为 3.3±0.6；平均复测 V T 值分别为 GM 中的 3.7±1.0，WM/NAWM 中的 3.3±0.9，MS 病变中的 3.3±0.7。测试 - 再测试结果显示 GM、WM/NAWM 和 MS 病变中 TRV 的平均绝对范围为 7-9%。GM 中高亲和力结合物的 V T 比中亲和力结合物高 30%。在活动性 MS 患者的两个增强病变中检测到局灶性（11）C-PBR28 摄取。
高分辨率（11）C-PBR28 PET 可以可视化已知小胶质细胞激活的局灶区域，并且在人脑中有良好的测试 - 再测试再现性。（11）C-PBR28 PET 可能对监测 MS 疾病演变和对靶向小胶质细胞激活的治疗策略的反应都很有价值。
