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• W2401720165 abstract "Optical fluorescence imaging is increasingly being used to monitor biological functions of specific targets (1-3). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350–700 nm) are used. Near-infrared (NIR) fluorescence (700–1,000 nm) detection avoids the natural background fluorescence interference of biomolecules, providing a high contrast between target and background tissues in small animals. NIR fluorophores have a wider dynamic range and minimal background fluorescence as a result of reduced scattering compared with visible fluorescence detection. NIR fluorophores also have high sensitivity, attributable to low background fluorescence, and high extinction coefficients, which provide high quantum yields. The NIR region is also compatible with solid-state optical components, such as diode lasers and silicon detectors. NIR fluorescence imaging is a non-invasive alternative to radionuclide imaging in small animals or with probes in close proximity of the target in humans (4, 5). Among the various optical imaging agents, only indocyanine green ( ICG ), with NIR fluorescence absorption at 780 nm and emission at 820 nm, is approved by the United States Food and Drug Administration for clinical applications in angiography, blood flow evaluation, and liver function assessment. It is also under evaluation in several clinical trials for other applications, such as optical imaging and mapping of both the lymphatic vessels and lymph nodes in cancer patients for surgical dissection of tumors and endoscopic imaging of the pancreas and colon.Integrins are a family of cell-surface heterodimeric glycoproteins that mediate diverse biological events involving cell–cell and cell–matrix interactions (6). They consist of an α and a β subunit, and they are important for cell adhesion and signal transduction. The αvβ3 integrin is the most prominent receptor class affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (7-12). The αvβ3 integrin is strongly expressed on tumor cells and activated endothelial cells. In contrast, expression of αvβ3 integrin is weak on resting endothelial cells and most normal tissues. The αvβ3 antagonists are being studied as anti-tumor and anti-angiogenic agents (9, 13, 14), and the agonists are being studied as angiogenic agents for coronary angiogenesis (15, 16). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including αvβ3. Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (17).Cyclo(RGDyK) was conjugated with Cy5.5 to study in vivo biodistribution of the tracer in tumor-bearing mice. Cy5.5 is a NIR fluorescent dye with an absorbance maximum at 675 nm and an emission maximum at 694 nm, with a high extinction coefficient of 250,000 (mol/L)–1cm–1. c(RGDyK)-Cy5.5 was found to have high and long-lasting accumulation in αvβ3-positve U87MG human glioblastoma tumor cells in nude mice (18). The binding of c(RGDyK)-Cy5.5 to the integrin receptor was found to be specific both in vitro and in vivo. von Wallbrunn et al. (19) performed optical NIR fluorescence imaging studies using a two-dimensional planar fluorescence reflectance imaging system and three-dimensional fluorescence-mediated tomography (FMT) of cyclo(Cys-Arg-Gly-Asp-Cys)-Gly-Lys-Cy5.5 (c(CRGDC)-GK-Cy5.5) in tumor-bearing nude mice." @default.
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• W2401720165 date "2012-02-02" @default.
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• W2401720165 title "Cyclo(Cys-Arg-Gly-Asp-Cys)-Gly-Lys-Cy5.5" @default.
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