Atherosclerosis

Molecular Imaging of Inflammation in Atherosclerosis

Inflammation is thought to be a hallmark of the progression of atherosclerotic plaque toward an unstable phenotype. Several cell surface markers have been shown to be useful for imaging inflammation in the context of plaque development in research animals. Of particular interest is the cell adhesion molecule VCAM-1, which is highly expressed on inflamed endothelial cells.

In the experiment below, Targestar® SA labeling contrast agent was conjugated to an anti-VCAM-1 antibody or an isotype-matched specificity control antibody. Contrast agents were administered to ApoE-/- or age-matched wild type control mice, and were imaged along the plane of the right common carotid artery, such that the ascending aorta, innominate artery, and common carotid were all visible. Each mouse (n=6) received targeted and to accumulate over 18 minutes. Mice control agents in random order. Significant enhancement was observed within the principle arteries in the field of view using VCAM-1 targeted agents in the ApoE-/- mice. Accumulation of the contrast agents corresponded to regions in which atherosclerotic plaque and VCAM-1 expression is found.

Figure 2. Color Doppler (top left) delineates the location of the principle arteries. Middle image shows contrast signal from VCAM-1 targeted agents, while bottom image shows low retention of control agents. 

Imaging Angiogenesis in Atherosclerosis

Recent work has suggested a link between atherogenesis and the growth of new blood vessels. Although the significance of angiogenic activity is not yet certain, development of a well-perfused vasa vasorum within a plaque may have relevance to plaque progression or response to treatment. In the experiment below, Targestar SA was conjugated to an anti-VEGFR2 antibody or isotype specificity control. Contrast agents were administered to an ApoE-/- mouse or healthy age-matched control mouse, and contrast agent retention within the innominate artery and ascending aortic arch was measured. A strong contrast signal was observed for VEGFR2-targeted agents in regions of plaque formation in the ApoE mouse, but not in the healthy mouse.