| 20128995 |
Liu Z, Liu S, Niu G, Wang F, Liu S, Chen X: Optical imaging of integrin alphavbeta3 expression with near-infrared fluorescent RGD dimer with tetra (ethylene glycol) linkers. Mol Imaging. 2010 Feb;9(1):21-9.
Integrin alphavbeta3 plays great roles in tumor angiogenesis, invasion, and metastasis. We report here the noninvasive visualization of tumor integrin alphavbeta3 expression by using near-infrared fluorescence (NIRF) imaging of an IRDye800-labeled new cyclic RGD (arginine-glycine-aspartic acid) dimer with tetra (ethylene glycol) (PEG4) linkers (ie, E [PEG4-c (RGDfK)] 2, PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) in a U87MG tumor model. Fluorescent dye-labeled E [PEG4-c (RGDfK)] 2 were subjected to in vitro cell staining, in vivo NIRF imaging, ex vivo NIRF imaging, and histologic studies. The in vitro and in vivo characterization of dye-labeled E [PEG4-c (RGDfK)] 2 were compared with dye-labeled RGD dimer without PEG4 linkers (namely, E [c (RGDfK)] 2). Both Cy5.5-E [PEG4-c (RGDfK)] 2 and Cy5.5-E [c (RGDfK)] 2 exhibited integrin alphavbeta3 binding specificity in a cell-staining experiment. In vivo NIRF imaging showed higher tumor accumulation and tumor to background contrast of IRDye800-E [PEG4-c (RGDfK)] 2 over IRDye800-E [c (RGDfK)] 2. The tumor integrin alphavbeta3 specificity of IRDye800-E [PEG4-c (RGDfK)] 2 was confirmed by successful inhibition of tumor uptake in the presence of an excess dose of c (RGDfK). Histologic examination revealed both tumor vasculature and tumor cell integrin alphavbeta3 binding of IRDye800-E [PEG4-c (RGDfK)] 2 in vivo. In summary, NIRF imaging with IRDye800-E [PEG4-c (RGDfK)] 2 offers an easy, fast, and low-cost way to detect and semiquantify tumor integrin alphavbeta3 expression in living subjects. |
34(0,1,1,4) |