Department of Neurology, University Medical Centre Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Parkinsonism Relat Disord. 2010 Jan;16(1):57-9. doi: 10.1016/j.parkreldis.2009.05.005. Epub 2009 May 31.
[(11)C]-PK11195 PET has been used for in vivo brain imaging of microglia activation in Parkinson's disease (PD) patients. COX-2 inhibition has been shown to reduce neuroinflammation and neurodegeneration in animal models of PD. This pilot study assessed the use of [(11)C]-PK11195 PET to quantify neuroinflammation and evaluate the ability of COX-2 inhibition to reduce neuroinflammation in PD patients.
Fourteen PD patients and eight healthy, age matched controls underwent a [(11)C]-PK11195 PET and MRI scan. Five PD patients were scanned before and after one month of celecoxib treatment 200 mg/day. Arterial plasma sampling and metabolite analysis were performed to create plasma input curves. A 2-compartment model and Logan analysis were applied and parametric DV images were compared using t-test in SPM2. In addition a simplified reference region model (SRTM) was applied, with both the cerebellum and a reference region derived from cluster analysis.
Using the cluster analysis, PD patients showed higher contralateral putamen BP and midbrain BP compared to controls, although considerable overlap was seen and differences were not statistically significant. Unexpectedly, BP and DV after celecoxib were slightly higher. Cerebellum as reference region resulted in lower BP values and k(3)/k(4) gave 10-fold higher BP values. Linearization of the data did not show differences between PD patients and controls.
In current practice, [(11)C]-PK11195 seems an unsuitable tracer for accurate or reliable quantification of neuroinflammation. Refinement of [(11)C]-PK11195 uptake analysis and, more importantly, further development of better tracers is necessary to enable accurate measurement of neuroinflammation and effects of anti-inflammatory treatment in patients.
[(11)C]-PK11195 PET 已用于帕金森病 (PD) 患者的脑内小胶质细胞激活的体内成像。COX-2 抑制已被证明可减少 PD 动物模型中的神经炎症和神经退行性变。本研究旨在评估 [(11)C]-PK11195 PET 用于量化神经炎症，并评估 COX-2 抑制减少 PD 患者神经炎症的能力。
14 名 PD 患者和 8 名年龄匹配的健康对照者接受 [(11)C]-PK11195 PET 和 MRI 扫描。5 名 PD 患者在接受 COX-2 抑制剂塞来昔布治疗 1 个月（200mg/天）前后进行扫描。进行动脉血浆取样和代谢物分析以创建血浆输入曲线。应用 2 室模型和 Logan 分析，并在 SPM2 中使用 t 检验比较参数 DV 图像。此外，还应用了简化参考区模型 (SRTM)，使用小脑和聚类分析得到的参考区。
使用聚类分析，PD 患者的对侧壳核和中脑 BP 高于对照组，但存在相当大的重叠，差异无统计学意义。出乎意料的是，塞来昔布后的 BP 和 DV 稍高。小脑作为参考区导致 BP 值降低，k(3)/k(4) 给出 10 倍高的 BP 值。数据的线性化未显示 PD 患者与对照组之间的差异。
在当前实践中，[(11)C]-PK11195 似乎不适合用于准确或可靠地量化神经炎症。需要改进 [(11)C]-PK11195 摄取分析，更重要的是，需要进一步开发更好的示踪剂，以实现对患者神经炎症和抗炎治疗效果的准确测量。
