Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging

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

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 [11C]-PK11195 have provided inconclusive results. Here we assess the presence and distribution of neuroinflammatory response in PD patients using [18F]-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 [18F]-DPA714 and [11C]-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 [18F]-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 [11C]-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: [18F]-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.

Keywords: Microglia; Neuroinflammation; PET; Parkinson disease; TSPO; [(18)F]-DPA714.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Disease Progression*
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / metabolism*
  • Humans
  • Inflammation* / diagnostic imaging
  • Inflammation* / immunology
  • Inflammation* / metabolism
  • Male
  • Mesencephalon / diagnostic imaging
  • Mesencephalon / metabolism*
  • Microglia / metabolism*
  • Middle Aged
  • Nortropanes / pharmacokinetics
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / immunology*
  • Parkinson Disease / metabolism*
  • Positron-Emission Tomography
  • Putamen / diagnostic imaging
  • Putamen / metabolism*
  • Pyrazoles / pharmacokinetics
  • Pyrimidines / pharmacokinetics
  • Receptors, GABA / metabolism*
  • Time Factors

Substances

  • Fluorine Radioisotopes
  • N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
  • N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane
  • Nortropanes
  • Pyrazoles
  • Pyrimidines
  • Receptors, GABA
  • TSPO protein, human
  • Fluorine-18

Associated data

  • ClinicalTrials.gov/NCT02319382