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MICID

Molecular Imaging in Chronic Inflammatory Diseases
Funder: French National Research Agency (ANR)Project code: ANR-24-CE17-1725
Funder Contribution: 453,488 EUR
Description

Single domain antibodies (sdAb or nanobodies) based imaging agent directed at the inflammatory marker Vascular Cell Adhesion Molecule 1 (VCAM-1) have recently been validated by the LRB (partner 1) for the non-invasive nuclear imaging of atherosclerosis and liver inflammation in mice. The lead compound (cAbVCAM1-5) has been produced according to good manufacturing practice and a phase I/II clinical trial is underway at Grenoble-Alpes University Hospital. The aim of the present project is to further evaluate its capabilities using preclinical mice models in order to pave the way of future clinical evaluations. To fulfill this objective, we will evaluate its ability to detect and quantify chronic inflammation in various pathological settings and organs. Moreover, we will evaluate the potency of anti-VCAM-1 sdAb for magnetic resonance imaging (MRI), as an alternative to nuclear imaging, using biodegradable microparticles developed by partner 4 (PhIND). cAbVCAM1-5 will therefore be evaluated in a mouse model of spondyloarthritis in collaboration with the T-Raig team (Lab TIMC, partner 2), in mice models of myocardial infarction with HP2 laboratory (partner 3) and in mice models of neuroinflammation in collaboration with PhIND. Upon completion of this research project, the consortium will have investigated the potential of the anti-VCAM-1 sdAb in 3 pathological settings that could potentially benefit from improved diagnostic and prognostic imaging biomarkers for the management of patients. The results will therefore allow determining relevant strategies for the evaluation of this novel imaging agent, in particular for the design of phase II clinical trials. Moreover, it will provide a better understanding of the tissue and subcellular distribution of this imaging agent, and will explore the possibility to extend its field of application using MRI as a second imaging modality.

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