Molecular imaging of microglial activation in amyotrophic lateral sclerosis

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.

Figure 1. Parametric (DVR) 18F-DPA-714 images (axial, coronal and sagittal slices) obtained for a healthy volunteer and an ALS patient, respectively.

Note the significant but normal 18F-DPA-714 uptake in nasal epithelium (a tissue rich in TSPO).

Figure 2. Individual DVR values for the two motor cortex regions and the temporal cortex obtained for all subjects.

These are the regions where statistically significant differences were observed between the two groups studied.