O230	Antibody conjugated near infrared dye detects focal atherosclerotic lesions in ApoE deficient mice.
1M.Roser, 2Chr.Perlitz, 1M.Gräfe, 1T.Dietrich, 1K.Atrott, 1Ph.Stawowy, 1E.Nagel, 1E.Fleck, 2M.Schirner, 1K.Graf
1Deutsches Herzzentrum, Berlin, DE; 2Schering AG, Berlin, DE.

The aim of this study was to examine the expression of ED-B fibronectin in a murine model of moderate atherosclerosis to investigate its relevance for imaging of early atherosclerotic lesions. Apolipoprotein-E-null (ApoE-/-) mice and control mice (C57Bl6) were fed with normal chow up to 10 months, leading to modest focal atherosclerosis in the aortic arch and the supraaortic arteries. Sudan red staining and immunohistochemical analysis of the vessel wall using antibodies against ED-B (AP39), CD31, CD68 and actin was performed in mice at age 3, 7 and 10 months (n=15). ED-B immunoreactivity was observed in focal atherosclerotic lesions, but absent in non-atherosclerotic arteries or control animals. Histomorphometry revealed correlation of ED-B expression with the increase in atherosclerotic plaque lesion size and number. Immunohistochemical analysis revealed strong interstitial immmunoreactivity and identified mainly smooth muscle and endothelial cells as ED-B positive cells. In contrast, no immunoreactivity was detected in control mice and in wall areas free of atherosclerosis in younger ApoE mice. Imaging for atherosclerotic plaques in-vivo was performed with AP39 anti ED-B, labeled with near infrared (NIR) fluorophores and injected intravenously into atherosclerotic ApoE-/- (n = 14) or normal wild-type mice (n = 4) at the age of 10 months. Mice were killed 24 hours after injection and NIR fluorescence was analysed in thoracic aorta and supraaortic arteries. NIR-signals demonstrated a strong intensity in focal plaque lesions, whereas no signal was found in undiseased aortas from control mice or in mice injected unspecific NIR fluorophores (n=3). NIR-signal positive areas increased with animal age and correlated with the increase of histological observed plaque size. Conclusion: This study demonstrates that plaque imaging using antibodies labelled with near infrared fluorophores is feasible in a model of focal atherosclerosis.

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