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Visualizing Neuroinflammation in the Brain

​How could we observe the neuroinflammation mechanisms in the development of neurodegenerative diseases? A team from the CEA Frédéric-Joliot Institute has been testing tracers for PET imaging.

Published on 3 April 2017
Neuroinflammation is a cerebral immunity mechanism that is meant to protect the brain from aggression. Although it has been observed in neurodegenerative diseases, its role is complex, so much so that some scientists call it "Dr Jekyll and Mr Hyde". For example, neuroinflammation appears to play a protective role in the early stages of Alzheimer's disease, yet it has a harmful effect in its more advanced stages.

Brain neuroinflammation is driven by glial cells—the cells that form the environment of neurons. To better understand the underlying mechanisms, scientists are developing specific molecular tracers for imaging. "Currently, marker [18F]DPA-714 is very popular among scientists," said Alexandra Winkeler from the Frédéric-Joliot Life Sciences Institute. "It targets TSPO, a protein that is overexpressed in neuroinflammation." Other proteins are also of interest to researchers—the CB2R cannabinoid receptors in particular. "Although TSPO proteins are produced by different cell types, CB2Rs seem more promising because they would be specific to a single type of glial cells called microglia," Winkeler added.

In collaboration with a Spanish laboratory, a team from the Frédéric-Joliot Institute has tested a CB2R tracer for PET imaging (positron emission tomography) in three rodent models of neuroinflammation. "This tracer, called [11C] A-836339, was developed by radiochemists. The scientific community relies heavily on it," Winkeler said. Unfortunately, no binding of this tracer on CB2R is visible in PET imaging." Meanwhile, the same team revealed that following an anti-inflammatory treatment targeting CB2Rs, tracer [18F]DPA-714 showed a reduction in neuroinflammation. Thus, currently, there is no tracer better than DPA-714 for observation of neuroinflammation.

This work is part of European project INMiND, which aims to visualize and quantify neuroinflammation in neurodegenerative diseases.

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