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First published online October 16, 2008, 10.2967/jnumed.108.052514
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Journal of Nuclear Medicine Vol. 49 No. 11 1845-1851
© 2008 by Society of Nuclear Medicine
doi: 10.2967/jnumed.108.052514

Basic Science Investigation

Fluorescence Reflectance Imaging of Macrophage-Rich Atherosclerotic Plaques Using an {alpha}vβ3 Integrin–Targeted Fluorochrome

Jens Waldeck*,1, Florian Häger*,1, Carsten Höltke1,2, Christian Lanckohr3, Angelika von Wallbrunn1, Giovanni Torsello4, Walter Heindel1, Gregor Theilmeier5, Michael Schäfers2,6 and Christoph Bremer1,6

1 Department of Clinical Radiology, University Hospital Muenster, University of Muenster, Muenster, Germany; 2 Department of Nuclear Medicine, University Hospital Muenster, University of Muenster, Muenster, Germany; 3 Department of Anesthesiology and Intensive Care Medicine, University Hospital Muenster, University of Muenster, Muenster, Germany; 4 St. Franziskus Hospital, Muenster, Germany; 5 Department of Anesthesiology, Medical University of Hannover, Hannover, Germany; and 6 Interdisciplinary Center for Clinical Research (IZKF Muenster, FG3 TH69 and ZPG 4b), University Hospital Muenster, University of Muenster, Muenster, Germany

Correspondence: For correspondence or reprints contact: Jens Waldeck, Department of Clinical Radiology, University Hospital Muenster, University of Muenster, Haus Rosenbach, Waldeyerstrasse 1, 48149 Muenster, Germany. E-mail: waldeck{at}uni-muenster.de

Macrophages play an important role during the development and progression of atherosclerotic plaques. {alpha}vβ3 integrins are highly expressed by macrophages; thus, targeting {alpha}vβ3 may allow targeting of culprit macrophage-loaded atherosclerotic lesions in vivo. Methods: An {alpha}vβ3-targeted Arg-Gly-Asp (RGD) peptide was labeled with the cyanine 5.5 (Cy 5.5) dye and applied to image atherosclerotic plaques in apolipoprotein E–deficient mice. Results: The peptide–dye conjugate binds to {alpha}vβ3 integrin–positive RAW264.7 macrophages with high affinity. Competition experiments confirmed binding specificity of the probe. A significant fluorochrome accumulation in atherosclerotic plaques was demonstrated 24 h after injection by fluorescence reflectance imaging, which was blocked with high efficiency by competition with the unlabeled peptide. Conversely, the nonconjugated dye revealed only a minor fluorescence signal in the plaques. Fluorescence microscopy revealed colocalization of the probe with macrophages in the plaque of a mouse model for accelerated atherosclerosis, which was corroborated in human carotid artery specimens. In addition to macrophage-associated signals, binding of the probe to the neointima or elastica of the arteries was observed. Conclusion: RGD-Cy 5.5, combined with near-infrared optical imaging methods, allows the specific imaging of {alpha}vβ3-integrin expression on macrophages recruited to vascular lesions and may serve to estimate macrophage-bound inflammatory activity of atherosclerotic lesions.

Key Words: atherosclerotic plaque • optical imaging • {alpha}vβ3 integrin • RGD-Cy 5.5 • fluorescence reflectance imaging

* Contributed equally to this work.

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.


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