Molecular imaging of microglial activation in amyotrophic lateral sclerosis

PLoS One. 2012;7(12):e52941. doi: 10.1371/journal.pone.0052941. Epub 2012 Dec 31.

Abstract

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, (18)F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney's test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of (18)F-DPA-714 was increased in ALS patients during the "time of diagnosis" phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation.

Trial registration: ClinicalTrials.gov NCT00563537.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / diagnostic imaging*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Female
  • Humans
  • Inflammation / diagnostic imaging
  • Inflammation / metabolism
  • Male
  • Microglia / diagnostic imaging*
  • Microglia / metabolism
  • Middle Aged
  • Molecular Imaging
  • Neuroimaging
  • Radionuclide Imaging
  • Receptors, GABA / metabolism*

Substances

  • Receptors, GABA
  • TSPO protein, human

Associated data

  • ClinicalTrials.gov/NCT00563537

Grant support

This study was financially supported by the CHRU Tours (Grant NCT 00563537) and FEDER (“Radex” programme), Labex (Iron) and by the European Program FP7-HEALTH-2011 (INMiND-Imaging of Neuroinflammation in Neurodegenerative Diseases). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.