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Molecular imaging of microglial activation in amyotrophic lateral sclerosis
Philippe Corcia1, Clovis Tauber, Johnnie Vercoullie
1ALS Center, Department of Neurology, CHRU Bretonneau, Tours, France. corcia@med.univ-tours.fr
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.
Insights
Neuroinflammation is evident in amyotrophic lateral sclerosis (ALS) patients, indicated by increased microglial activation in the brain. The study utilized (18)F-DPA-714 PET imaging to detect this activation, offering potential as a biomarker.
Area of Science:
- Neuroscience
- Neurology
- Medical Imaging
Background:
- Amyotrophic lateral sclerosis (ALS) is associated with neuroinflammation, particularly microglial activation in the cerebral cortex.
- The 18 kDa translocator protein (TSPO) is upregulated in activated microglia and serves as a potential biomarker for neuroinflammation.
Purpose of the Study:
- To evaluate neuroinflammation in ALS patients by measuring microglial activation using the TSPO radioligand (18)F-DPA-714.
- To assess the potential of (18)F-DPA-714 as a biomarker for ALS pathophysiology and treatment efficacy.
Main Methods:
- Prospective PET study involving ten patients with probable or definite ALS and eight age-matched healthy controls.
- Participants were right-handed, without dementia, and not on medication that could affect TSPO binding.
- Distribution volume ratios of (18)F-DPA-714 were compared between ALS patients and controls using the Mann-Whitney's test.
Main Results:
- A significant increase in (18)F-DPA-714 uptake, indicating microglial activation, was observed in the primary motor, supplementary motor, and temporal cortex of ALS patients.
- Cortical uptake of (18)F-DPA-714 was elevated in ALS patients at the time of diagnosis.
Conclusions:
- Cortical microglial activation is present in ALS patients at diagnosis, as detected by (18)F-DPA-714 PET.
- This finding enhances understanding of ALS pathophysiology and suggests (18)F-DPA-714 may serve as a surrogate marker for treatment efficacy targeting microglial activation.
