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Content archived on 2024-05-29

Molecular imaging of Atherosclerosis

Objective

The leading cause of morbidity and mortality in developed nations is vascular disease such as cardiovascular disease and cerebrovascular disease. The process common to these diseases is atherosclerosis, and in particular, the formation of vulnerable plaques those rupture and cause thromboembolic disease1.

Therefore, there exists a need to develop a non-invasive strategy that can detect and assess vulnerable plaques prior to plaque rupture that can provide both high-resolution anatomic and functional information with a high degree of sensitivity and specificity. Myeloperoxidase (MPO) has been identified as a marker of active inflammation in vulnerable plaques.

Elevated plasma MPO concentrations have been found in stroke and myocardial infarction2. Thus, MPO i s evolving as a key molecular and clinical biomarker of vulnerable plaques. The Weissleder group has recently developed a novel approach for imaging peroxidases using low molecular weight paramagnetic enzyme substrates3.

The overall goal of this proposal i s to develop and test novel activatable molecular imaging agents that can sense MPO activity in vivo, and to expose the candidate to state of the art molecular imaging techniques in an integrated multidisciplinary environment.

These "smart" agents harness enzyme-mediated amplification and are potentially much more sensitive than alternative targeted agents. We hypothesize that MPO substrates are converted into highly reactive self-polymerizing intermediates that give oligomers with high relaxivity.

Preliminary data have shown that these novel agents can be used to report enzyme activity by MRI and nuclear medicine. 1. Libby P. Nature 2002;420(6917):868-874. 2. Brennan ML et al. N Engl J Med 2003;349(17):1595-1604. 3. Chen JW et al. Magn Reson Med 2004

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Call for proposal

FP6-2005-MOBILITY-6
See other projects for this call

Coordinator

SPANISH COUNCIL FOR SCIENTIFIC RESEARCH
EU contribution
No data

Participants (1)