Abstract 11535: A Triple-Targeting Strategy for Characterization of Plaque Inflammation in Mice and Humans Using Molecular Imaging

Abstract

Introduction: Molecular imaging using inflammatory markers might offer additional information for plaque characterization. Here, we present a novel triple-target imaging strategy for the diagnosis and characterization of inflamed plaques using antibodies against vascular cell adhesion molecule 1 (VCAM1), lectin-like ox-LDL receptor (LOX1), and glycoprotein VI (GPVI). Methods: Antibodies against VCAM1, LOX1, GPVI, as well as control antibodies were conjugated to three different fluorescent dyes for imaging with the IVIS spectrum. As a model of atherosclerosis, we used ApoE-/- mice which were divided into three groups and fed 3 months of western type diet (WTD), 6 months of WTD, or 3 months of WTD with daily high-dose atorvastatin, respectively. Afterwards, their aortic arches were removed and imaged after incubation with the antibodies. To transfer our findings into a human model, we use carotid endarterectomy specimens for IVIS as well as magnetic resonance imaging (MRI). For MRI, we coupled our antibodies to microparticles of iron oxide (MPIO), a hypo intense contrast agent, and imaged the plaques using a small animal 9.4 T MRI after incubation under flow conditions. Results: The VCAM1, LOX1, and GPVI antibody constructs showed specific binding to atherosclerotic plaques in mice (p<0.05 for all three; n=4-5 per group) at both time points in comparison with their controls. The additional treatment with Atorvastatin led to a reduction for the signals of all three receptors (all p<0.05). After 6 in comparison to 3 month of WTD, an increase of LOX1 (p<0.05), a reduction of VCAM1 (p<0.05) and no significant changes of GPVI (p=0,81) were seen. Perfusion of the endarterectomy specimens with the MPIO-labeled contrast agent led to a significant signal reduction in MRI in comparison with their controls (n=8 per group; VCAM1 p=0.02; GPVI p=0.03). Our preliminary data for LOX1 show a tendency towards reduction (n=4; p=0.15) while not reaching significance yet. Conclusion: In this approach, we apply a new strategy of molecular MRI by targeting three different inflammatory markers in murine and human atherosclerosis for the noninvasive characterization of this disease, which might help to improve early detection and therapy of vulnerable atherosclerotic plaques.