PT  - JOURNAL ARTICLE
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
TI  - Fluorescence Reflectance Imaging of Macrophage-Rich Atherosclerotic Plaques Using an α<sub>v</sub>β<sub>3</sub> Integrin–Targeted Fluorochrome
AID  - 10.2967/jnumed.108.052514
DP  - 2008 Nov 01
TA  - Journal of Nuclear Medicine
PG  - 1845--1851
VI  - 49
IP  - 11
4099  - http://jnm.snmjournals.org/content/49/11/1845.short
4100  - http://jnm.snmjournals.org/content/49/11/1845.full
SO  - J Nucl Med2008 Nov 01; 49
AB  - 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.