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Optical Imaging of Integrin α_vβ_3 Expression with Near-Infrared Fluorescent RGD Dimer with Tetra(ethylene glycol) Linkers

机译:使用四(乙二醇)接头的近红外荧光RGD二聚体对整合素α_vβ_3表达的光学成像。

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摘要

Integrin α_vβ_3 plays great roles in tumor angiogenesis, invasion, and metastasis. We report here the noninvasive visualization of tumor integrin α_vβ_3 expression by using near-infrared fluorescence (NIRF) imaging of an IRDye800-labeled new cyclic RGD (arginine-glycine-aspartic acid) dimer with tetratethylene glycol) (PEG_4) linkers (ie, E[PEG_4-c(RGDfK)]_2, PEG_4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) in a U87MG tumor model. Fluorescent dye-labeled E[PEG_4-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[PEG_4-c(RGDfK)]_2 were compared with dye-labeled RGD dimer without PEG_4 linkers (namely, E[c(RGDfK)]_2). Both Cy5.5-E[PEG_4-c(RGDfK)]_2 and Cy5.5-E[c(RGDfK)]_2 exhibited integrin α_vβ_3 binding specificity in a cell-staining experiment. In vivo NIRF imaging showed higher tumor accumulation and tumor to background contrast of IRDye800-E[PEG_4-c(RGDfK)]_2 over IRDye800-E[c(RGDfK)]_2. The tumor integrin α_vβ_3 specificity of IRDye800-E[PEG_4-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 α_vβ_3 binding of IRDye800-E[PEG_4-c(RGDfK)]_2 in vivo. In summary, NIRF imaging with IRDye800-E[PEG_4-c(RGDfK)]_2 offers an easy, fast, and low-cost way to detect and semiquantify tumor integrin α_vβ_3 expression in living subjects.
机译:整联蛋白α_vβ_3在肿瘤血管生成,侵袭和转移中起重要作用。我们在这里报告通过使用IRDye800标记的新的环状RGD(精氨酸-甘氨酸-天冬氨酸)二聚体与四甘醇(PEG_4)接头(即,E)的近红外荧光(NIRF)成像,对肿瘤整联蛋白α_vβ_3表达进行无创可视化在U87MG肿瘤模型中,[PEG_4-c(RGDfK)] _ 2,PEG_4 = 15-氨基-4,7,10,13-四氧杂十五烷酸。荧光染料标记的E [PEG_4-c(RGDfK)_] 2进行了体外细胞染色,体内NIRF成像,离体NIRF成像和组织学研究。将染料标记的E [PEG_4-c(RGDfK)] _ 2的体外和体内特性与不含PEG_4接头的染料标记的RGD二聚体(即E [c(RGDfK)] _ 2)进行了比较。 Cy5.5-E [PEG_4-c(RGDfK)] _ 2和Cy5.5-E [c(RGDfK)] _ 2在细胞染色实验中均表现出整联蛋白α_vβ_3的结合特异性。体内NIRF成像显示IRDye800-E [PEG_4-c(RGDfK)] _ 2比IRDye800-E [c(RGDfK)] _ 2具有更高的肿瘤蓄积度和肿瘤与背景的对比。 IRDye800-E [PEG_4-c(RGDfK)] _ 2的肿瘤整联蛋白α_vβ_3特异性是通过在过量c(RGDfK)的存在下成功抑制肿瘤摄取来证实的。组织学检查显示体内IRDye800-E [PEG_4-c(RGDfK)] _ 2的肿瘤脉管系统和肿瘤细胞整联蛋白α_vβ_3结合。总之,使用IRDye800-E [PEG_4-c(RGDfK)] _ 2进行的NIRF成像提供了一种简便,快速且低成本的方法,可以检测和半定量活体内肿瘤整合素α_vβ_3的表达。

著录项

  • 来源
    《Molecular imaging》 |2010年第1期|21-29|共9页
  • 作者单位

    Molecular Imaging Program at Stanford, Departments of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, Stanford, CA Medical Isotopes Research Center, Peking University, Beijing, China School of Health Sciences, Purdue University, IN Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD;

    Molecular Imaging Program at Stanford, Departments of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, Stanford, CA Medical Isotopes Research Center, Peking University, Beijing, China School of Health Sciences, Purdue University, IN Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD;

    Molecular Imaging Program at Stanford, Departments of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, Stanford, CA Medical Isotopes Research Center, Peking University, Beijing, China School of Health Sciences, Purdue University, IN Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD;

    Molecular Imaging Program at Stanford, Departments of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, Stanford, CA Medical Isotopes Research Center, Peking University, Beijing, China School of Health Sciences, Purdue University, IN Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD;

    Molecular Imaging Program at Stanford, Departments of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, Stanford, CA Medical Isotopes Research Center, Peking University, Beijing, China School of Health Sciences, Purdue University, IN Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD;

    Molecular Imaging Program at Stanford, Departments of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, Stanford, CA Medical Isotopes Research Center, Peking University, Beijing, China School of Health Sciences, Purdue University, IN Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD Laboratory of Molecular Imaging and Nanomedicine, NIBIB/CC/NIH, 31 Center Drive, 31/1C22, Bethesda, MD 20892-2281;

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  • 入库时间 2022-08-18 00:39:15

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