Abstract 2436: The Human Antibody against the C Domain of Tenascin-C images Murine Atherosclerotic Plaques ex vivo
Objective - The identification and targeting of proteins which are overexpressed in atherosclerotic plaques may open novel diagnostic and therapeutic applications. The extradomain C is typically absent in normal adult tissues, but can be inserted in the Tenascin-C molecule by alternative splicing. We tested the ability of the human antibody G11, specific to this antigen, to visualize murine atherosclerotic plaques ex vivo. The human antibody L19, directed against the extradomain B of fibronectin, was used as a reference.
Methods and Results - We intravenously injected 125Iodine-labeled preparations of G11 and L19 antibodies into apolipoprotein E knockout (ApoE−/−) mice and harvested the aortae 24 hours later. En face analyses of aortae revealed a significant correlation between radiolabeled G11 and fat stained (oil-red O) areas (r=0.87, P<0.0001) with an average signal-to-noise ratio of 69:1. Plaque imaging using L19 gave similar results (r=0.88, P<0.0001; signal-to-noise ratio 62:1). The uptake of the radiolabeled antibodies in histological sections colocalized with aortic plaques. Immunofluorescence analysis of aortic arch sections revealed expression of the tenascin and fibronectin isoforms in plaque regions with high density of macrophage infiltration.
Conclusions - The antibody G11, specific to the C domain of tenascin-C, selectively visualizes murine atherosclerotic plaques ex vivo. Given the increased expression of the C domain of tenascin-C in lipid- and macrophage-rich plaques and the high level of antigen conservation between mice and men, the G11 antibody may represent a useful tool for molecular imaging of vulnerable atherosclerotic plaques.