Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28

Neuroimage Clin. 2015 Jan 19;7:409-14. doi: 10.1016/j.nicl.2015.01.009. eCollection 2015.

Abstract

Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [(11)C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38-68 years) and ten age- and [(11)C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33-65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (p FWE < 0.05). Region of interest analysis revealed increased [(11)C]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15) compared to controls (1.03, p < 0.05). In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05), and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = -0.66, p < 0.05). Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [(11)C]-PBR28 as a marker of treatments that target neuroinflammation.

Keywords: ALS, amyotrophic lateral sclerosis; ALSFRS-R, amyotrophic lateral sclerosis functional rating scale revised; Amyotrophic lateral sclerosis; FWE, family-wise error rate; MR, magnetic resonance; Microglia; Motor cortex; Neuroinflammation; PBR-28, peripheral benzodiazepine receptor 28; PET, positron emission tomography; Positron emission tomography; SUV, standardized uptake value; TSPO, 18 kDa translocator protein; UMNB, upper motor neuron burden scale; VC, vital capacity.; [11C]PBR-28.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides*
  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / diagnostic imaging*
  • Brain / diagnostic imaging*
  • Carbon Radioisotopes
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuroglia / diagnostic imaging*
  • Positron-Emission Tomography / methods
  • Pyridines*
  • Radiographic Image Interpretation, Computer-Assisted
  • Radiopharmaceuticals*

Substances

  • Acetamides
  • Carbon Radioisotopes
  • N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide
  • Pyridines
  • Radiopharmaceuticals