RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 1845
OP 1851
DO 10.2967/jnumed.108.052514
VO 49
IS 11
A1 Jens Waldeck
A1 Florian Häger
A1 Carsten Höltke
A1 Christian Lanckohr
A1 Angelika von Wallbrunn
A1 Giovanni Torsello
A1 Walter Heindel
A1 Gregor Theilmeier
A1 Michael Schäfers
A1 Christoph Bremer
YR 2008
UL http://jnm.snmjournals.org/content/49/11/1845.abstract
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.