[11C]-PK11195 PET: Quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson's disease?
[11C]-PK11195 PET: Quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson's disease?
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DOI：
10.1016/j.parkreldis.2009.05.005
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发表时间：
2010-01-01
影响因子：
4.1
通讯作者：
Leenders, K. L.
中科院分区：
文献类型：
--
作者：
Bartels, A. L.;Willemsen, A. T. M.;Leenders, K. L.
[C-11]-PK11195 PET已用于帕金森病(PD)患者小胶质细胞激活的活体脑成像。抑制COX-2已被证明可以减少帕金森病动物模型的神经炎症和神经退行性变。这项初步研究评估了使用[C-11]-PK11195PET对PD患者的神经炎症进行量化和评估COX-2抑制治疗降低神经炎症的能力。方法：对14名PD患者和8名年龄匹配的健康对照进行了[C-11]-PK11195PET和MRI扫描。对5例PD患者在塞来昔布治疗前和治疗1个月后进行扫描，每次200 mg/d。进行动脉血浆采样和代谢物分析以创建血浆输入曲线。应用两室模型和Logan分析，用SPM2软件对参数DV图像进行t检验。结果：通过聚类分析，帕金森病患者的对侧壳核血压和中脑血压高于对照组，但有相当大的重叠，差异无统计学意义。出乎意料的是，塞来昔布治疗后的BP和DV略高。以小脑为参照区的BP值较低，而k(3)/k(4)的BP值高出10倍。结论：在目前的实践中，[C-11]-PK11195似乎不适合准确或可靠地定量测定神经炎症。需要改进[C-11]-PK11195摄取分析，更重要的是，进一步开发更好的示踪剂，以便能够准确测量患者的神经炎症和抗炎治疗的效果。(C)2009爱思唯尔有限公司。保留所有权利。
[C-11]-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 [C-11]-PK11195 PET to quantify neuroinflammation and evaluate the ability of COX-2 inhibition to reduce neuroinflammation in PD patients.Methods: Fourteen PD patients and eight healthy, age matched controls underwent a [C-11]-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.Results: 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.Conclusions: In current practice, [C-11]-PK11195 seems an unsuitable tracer for accurate or reliable quantification of neuroinflammation. Refinement of [C-11]-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. (C) 2009 Elsevier Ltd. All rights reserved.