TY - JOUR T1 - Fluorescence Reflectance Imaging of Macrophage-Rich Atherosclerotic Plaques Using an α<sub>v</sub>β<sub>3</sub> Integrin–Targeted Fluorochrome JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1845 LP - 1851 DO - 10.2967/jnumed.108.052514 VL - 49 IS - 11 AU - Jens Waldeck AU - Florian Häger AU - Carsten Höltke AU - Christian Lanckohr AU - Angelika von Wallbrunn AU - Giovanni Torsello AU - Walter Heindel AU - Gregor Theilmeier AU - Michael Schäfers AU - Christoph Bremer Y1 - 2008/11/01 UR - http://jnm.snmjournals.org/content/49/11/1845.abstract N2 - Macrophages play an important role during the development and progression of atherosclerotic plaques. αvβ3 integrins are highly expressed by macrophages; thus, targeting αvβ3 may allow targeting of culprit macrophage-loaded atherosclerotic lesions in vivo. Methods: An αvβ3-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 αvβ3 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 αvβ3-integrin expression on macrophages recruited to vascular lesions and may serve to estimate macrophage-bound inflammatory activity of atherosclerotic lesions. ER -