Targeted CEU Imaging of Atherosclerosis and Angiogenesis

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DESCRIPTION (provided by applicant): Non-invasive methods for imaging molecular and cellular processes could positively impact medicine in many ways. Such a method could be used to characterize disease pathophysiology, to diagnose disease at a very early stage, and to assess new therapeutic strategies. The overall aim of this proposal is to investigate novel methods for imaging molecular and cellular mediators of atherosclerosis and angiogenesis with contrast-enhanced ultrasound (CEU) in clinically-relevant models of disease. For imaging atherosclerosis, microbubble contrast agents targeted against the endothelial cell adhesion molecules VCAM-1 and P-selectin have been developed in order to image the vascular inflammatory processes that contribute to atherogenesis and plaque instability. Targeted CEU imaging with these agents will be performed in wild-type and Apo-E-deficient mice of different ages, with and without cholesterol feeding, which provides a model of progressive, inflammatory atherosclerosis similar to that found in humans. These data will determine whether targeted CEU can be used to assess atherosclerotic inflammatory phenotype, and to detect very early lesion development. For spatially and temporally assessing angiogenesis, CEU with microbubbles targeted to the integrin alpha-v beta-3 expressed by the neovascular endothelium, and to activated monocytes that participate in angiogenesis, will be applied in a rat ischemic hindlimb model of severe peripheral vascular disease. The ability to assess pro-angiogenic therapy with FGF-2 will also be determined in this model. Successful completion of these studies will provide the basis for a new non-invasive diagnostic technique capable of imaging the molecular mediators of atherosclerosis and angiogenesis. This technique may have a major impact for diagnosis and assessing response to therapy. CEU can be performed rapidly and relies on relatively inexpensive and widely available imaging technology, making it well-suited for clinical applications and for high-throughput screening in the laboratory. (End of Abstract)