UNLABELLED: Macrophages play an important role during the development and progression of atherosclerotic plaques. alphavbeta3 integrins are highly expressed by macrophages; thus, targeting alphavbeta3 may allow targeting of culprit macrophage-loaded atherosclerotic lesions in vivo. METHODS: An alphavbeta3-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 alphavbeta3 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 alphavbeta3-integrin expression on macrophages recruited to vascular lesions and may serve to estimate macrophage-bound inflammatory activity of atherosclerotic lesions.
UNLABELLED: Macrophages play an important role during the development and progression of atherosclerotic plaques. alphavbeta3 integrins are highly expressed by macrophages; thus, targeting alphavbeta3 may allow targeting of culprit macrophage-loaded atherosclerotic lesions in vivo. METHODS: An alphavbeta3-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-deficientmice. RESULTS: The peptide-dye conjugate binds to alphavbeta3 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 alphavbeta3-integrin expression on macrophages recruited to vascular lesions and may serve to estimate macrophage-bound inflammatory activity of atherosclerotic lesions.
Authors: Masahiro Terashima; Masaki Uchida; Hisanori Kosuge; Philip S Tsao; Mark J Young; Steven M Conolly; Trevor Douglas; Michael V McConnell Journal: Biomaterials Date: 2010-11-11 Impact factor: 12.479
Authors: Helen Su; Natalia Gorodny; Luis Felipe Gomez; Umesh B Gangadharmath; Fanrong Mu; Gang Chen; Joseph C Walsh; Katrin Szardenings; Daniel S Berman; Hartmuth C Kolb; Balaji K Tamarappoo Journal: J Nucl Cardiol Date: 2014-03-14 Impact factor: 5.952
Authors: Antti Saraste; Iina Laitinen; Eliane Weidl; Moritz Wildgruber; Axel W Weber; Stephan G Nekolla; Gabriele Hölzlwimmer; Irene Esposito; Axel Walch; Pia Leppänen; Irina Lisinen; Peter B Luppa; Seppo Ylä-Herttuala; Hans-Jürgen Wester; Juhani Knuuti; Markus Schwaiger Journal: J Nucl Cardiol Date: 2012-04-20 Impact factor: 5.952