TRIGLITEP project for "Development of PET ligands targeting glial cells: an immunomagnetic cell-sorting approach" aims to overcome a major bottleneck in brain imaging: the biological validation of neuroinflammation biomarkers.
Neuroinflammation, common to many disorders of the nervous system, involves a complex interplay between microglial cells and astrocytes. Positron emission tomography (PET) can visualize these processes using radiotracers, but the markers available so far, such as those targeting the TSPO protein, do not distinguish between different glial cell types or their activation states.
The TRIGLITEP project aims, in parallel with the standard development and validation of new PET radioligands capable of selectively targeting microglia or astrocytes, to develop approaches that provide a deeper understanding of the underlying biology of the target. One of these approaches focuses on identifying the cell-type specificity of these new targets. CEA teams are exploring several innovative strategies, such as correlating radioligand binding with the cellular expression of the target (with RNAscope), or measuring marker binding at the cellular level using immunomagnetic brain cell sorting. This method allows the imaging signals observed in PET to be directly linked to the biological reality of the target cells, but it requires radioligands that cross the blood - brain barrier and are labeled with fluorine-18, whose longer half-life makes these ex vivo analyses feasible. The first compounds developed by BioMaps target the purinergic receptor P2RY12, a microglia-specific marker. In parallel, the LMN uses animal models in which the target is overexpressed using a viral vector to assess the specificity and biological relevance of these new biomarkers.
By combining radiochemistry, neurobiology, and imaging, TRIGLITEP exemplifies the interdisciplinary momentum fostered by the CNRS PRIME program. This collaboration between BioMaps and the LMN in MIRCen Department contributes to the emergence of a new generation of more precise PET markers, paving the way for a better understanding of the mechanisms of neuroinflammation, which play a major role in neurodegenerative diseases and other neurological conditions.
Contact : Nadja Van Camp