使用 [F]-DPA714 TSPO PET 成像技术观察到帕金森病患者的小胶质细胞激活增加。

Increased microglial activation in patients with Parkinson disease using [F]-DPA714 TSPO PET imaging.

机构信息

Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives, 92265, Fontenay-aux-Roses, France.

Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Service Hospitalier Frédéric Joliot, 4, Place du Général Leclerc, Orsay, 91401, France.

出版信息

Parkinsonism Relat Disord. 2021 Jan;82:29-36. doi: 10.1016/j.parkreldis.2020.11.011. Epub 2020 Nov 17.

DOI:10.1016/j.parkreldis.2020.11.011

PMID:33242662

Abstract

INTRODUCTION

Increasing evidence suggests that neuroinflammation is active in Parkinson disease (PD) and contributes to neurodegeneration. This process can be studied in vivo with PET and radioligands targeting TSPO, upregulated in activated microglia. Initial PET studies investigating microglial activation in PD with the [C]-PK11195 have provided inconclusive results. Here we assess the presence and distribution of neuroinflammatory response in PD patients using [F]-DPA714 and to correlate imaging biomarkers to dopamine transporter imaging and clinical status.

METHODS

PD patients (n = 24, Hoehn and Yahr I-III) and 28 healthy controls were scanned with [F]-DPA714 and [C]-PE2I and analyzed. They were all genotyped for TSPO polymorphism. Regional binding parameters were estimated (reference Logan graphical approach with supervised cluster analysis). Impact of TSPO genotype was analyzed using Wilcoxon signed-rank test. Differences between groups were investigated using a two-way ANOVA and Tukey post hoc tests.

RESULTS

PD patients showed significantly higher [F]-DPA714 binding compared to healthy controls bilaterally in the midbrain (p < 0.001), the frontal cortex (p = 0.001), and the putamen contralateral to the more clinically affected hemibody (p = 0.038). Microglial activation in these regions did not correlate with the severity of motor symptoms, disease duration nor putaminal [C]-PE2I uptake. However, there was a trend toward a correlation between cortical TSPO binding and disease duration (p = 0.015 uncorrected, p = 0.07 after Bonferroni correction).

CONCLUSION

[F]-DPA714 binding confirmed that there is a specific topographic pattern of microglial activation in the nigro-striatal pathway and the frontal cortex of PD patients.

TRIAL REGISTRATION

Trial registration: INFLAPARK, NCT02319382. Registered 18 December 2014- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02319382.

摘要

简介

越来越多的证据表明，神经炎症在帕金森病（PD）中活跃，并导致神经退行性变。可以使用正电子发射断层扫描（PET）和针对 TSPO 的放射性配体来研究该过程，TSPO 在激活的小胶质细胞中上调。使用 [C]-PK11195 进行的最初 PET 研究对 PD 患者的小胶质细胞激活提供了不确定的结果。在这里，我们使用 [F]-DPA714 评估 PD 患者中神经炎症反应的存在和分布，并将成像生物标志物与多巴胺转运蛋白成像和临床状况相关联。

方法

对 24 名 PD 患者（Hoehn 和 Yahr I-III）和 28 名健康对照者进行了 [F]-DPA714 和 [C]-PE2I 扫描和分析。他们都进行了 TSPO 多态性基因分型。使用参考 Logan 图形方法进行了区域结合参数的估计（带监督聚类分析）。使用 Wilcoxon 符号秩检验分析了 TSPO 基因型的影响。使用双向方差分析和 Tukey 事后检验比较了两组之间的差异。

结果

与健康对照组相比，PD 患者双侧中脑（p < 0.001）、额叶皮层（p = 0.001）和对侧壳核（p = 0.038）的 [F]-DPA714 结合显著升高。这些区域的小胶质细胞激活与运动症状的严重程度、疾病持续时间或壳核 [C]-PE2I 摄取均无相关性。然而，皮质 TSPO 结合与疾病持续时间之间存在相关性的趋势（未校正时 p = 0.015，校正后 p = 0.07）。