TecSan - TecSan : Technologies pour la santé et l’autonomie

Molecular imaging of vulnerable atherosclerotic plaque – PLAQUIMAG

Submission summary

Cardiovascular diseases now represent the first cause of mortality worldwide, causing more deaths than cancer and respiratory diseases.Among cardiovascular diseases, coronary artery disease is responsible for more than half of cardiovascular deaths. Results from recent clinical and experimental studies have provided insights into the mechanisms of coronary artery disease development. It is now recognized that myocardial infarction is caused by the rupture of a coronary vulnerable atherosclerotic plaque, and that the diagnostic tool used for the detection of coronary artery disease, i.e. coronarography, is unappropriate. Indeed, coronarography does not allow the detection of vulnerable coronary atherosclerotic plaques responsible for most fatal cardiac events. Therefore, there is currently no imaging methodology available for the routine clinical detection of vulnerable atherosclerotic plaques on large populations of patients. Such a methodology would however greatly enhance the quality of at-risk patient care. It would also significantly decrease the total cost
of cardiovascular disease management.
Nuclear imaging is a molecular imaging technique that relies on the intravenous injection of a radiolabeled tracer which is used to specifically identify a molecular target or a physiological process. Gamma-cameras are used to provide images of whole-body tracer uptake. The sensitivity together with the functional nature of nuclear imaging make this methodology an excellent potential candidate for the development of a non-invasive tool for the detection of vulnerable atherosclerotic plaques. The molecular target that was previously identified by the INSERM U877 laboratory for the development of a specific tracer of vulnerable plaques is the adhesion molecule VCAM-1. Among all VCAM-1 potential tracers that have been experimentally evaluated, extremely promising results were obtained using 99mTc-EP43. Indeed, 99mTc-EP43 biodistribution indicated high tracer uptake in experimental atherosclerotic lesions together with low
circulating blood activity, thereby enabling the imaging of VCAM-1 expression in vivo. Based on these very promising experimental results, clinical studies are now warranted to determine the potential of EP43 for the non invasive detection of vulnerable atherosclerotic plaques in patients. SPECT and PET cameras are equally developed and commercialized. The SPECT modality, which mainly uses 99mTc, allows the manufacturing of an unlabeled kit in a single production site. The kit is then distributed worlwide and used for 99mTc radiolabeling in Nuclear Medicine Departments. On the other hand, it is widely acknowledged that the TEP modality (18F radiolabeling) has greater sensitivity when compared with SPECT. The clinical evaluation of EP43 will therefore be performed using both the SPECT and PET modalities. Overall, the problem addressed by the present project is the transfer of a non invasive imaging methodology allowing the identification of coronary vulnerable atherosclerotic plaques from the experimental to the clinical area. Such a technique would allow
the early identification of those patients with high coronary risk and their assignment to surgery or medical therapy prior to the occurrence of a major cardiac event. The setting of the present project is therefore both industrial and clinical.

Project coordination

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


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Beginning and duration of the scientific project: - 0 Months

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