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

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.

• Authors: Michael Fiechter, Katharina Frey, Tim Fugmann, Philipp A Kaufmann, Dario Neri
• Journal: Atherosclerosis (Atherosclerosis) Vol. 214 Issue 2 Pg. 325-30 (Feb 2011) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 21167484 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Apolipoproteins E
• Fibronectins
• Iodine Radioisotopes
• Tenascin
• Matrix Metalloproteinases
• Fluorescein

Topics

• Animals
• Antibodies, Monoclonal (biosynthesis, genetics, metabolism)
• Aorta (immunology)
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (immunology)
• Autoradiography
• CHO Cells
• Cricetinae
• Cricetulus
• Disease Models, Animal
• Fibronectins (immunology)
• Fluorescein
• HEK293 Cells
• Humans
• Imaging, Three-Dimensional
• Iodine Radioisotopes
• Male
• Matrix Metalloproteinases (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microscopy, Fluorescence
• Tenascin (immunology)