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Comparative in vivo analysis of the atherosclerotic plaque targeting properties of eight human monoclonal antibodies.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2011
Author Fiechter Michael, Frey Katharina, Fugmann Tim, Kaufmann Philipp A, Neri Dario, Veltman Caroline E, de Roos Albert, Pazhenkottil Aju, Kroft Lucia J, Boersma Eric, Herzog Bernhard, Leung Melissa, Maffei Erica, Leung Dominic Y, Kaufmann Philipp A, Cademartiri Filippo, Bax Jeroen J, Jukema J Wouter,
Project Entwicklung einer neuen Hybrid-Bildgebungs-Methode zur nicht invasiven kardialen Diagnostik
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Original article (peer-reviewed)

Journal Atherosclerosis
Volume (Issue) 214(2)
Page(s) 325 - 330
Title of proceedings Atherosclerosis
DOI 10.1016/j.atherosclerosis.2010.11.027

Abstract

OBJECTIVE The selective in vivo localization of antibody derivatives in atherosclerotic plaques may open novel diagnostic and therapeutic applications. Here, we present a comparative in vivo localization analysis of eight radioiodinated human monoclonal antibodies in apolipoprotein E-deficient (ApoE(-/-)) mice. METHODS Animals were fed with a cholesterol-rich diet, followed by harvesting of the aorta 24h after intravenous antibody injection and investigated by autoradiographic analysis. Localization of F8 antibody on atherosclerotic plaque structures was further studied in three-color fluorescence microscopy. RESULTS The study revealed that the F8 antibody, specific to the alternatively spliced EDA domain of fibronectin, exhibited the highest plaque-targeting potential among the antibodies analyzed in this study, with an ability to preferentially localize to all plaques within the aorta. Targeting results were confirmed by injection of fluorescein-labeled F8 antibody, followed by three-color fluorescence microscopy analysis. CONCLUSION These findings open novel biomolecular avenues for the in vivo imaging of atherosclerotic plaques and for pharmacodelivery applications, since F8 had previously been reported by our group to strongly stain atherosclerotic plaques in human carotid arteries.
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