title: Integrin αvβ3-targeted dynamic contrast-enhanced magnetic resonance imaging using a gadolinium-loaded polyethylene gycol-dendrimer-cyclic RGD conjugate to evaluate tumor angiogenesis and to assess early antiangiogenic treatment response in a mouse xenograft tumor model.
abstract: The purpose of this study was to validate an integrin αvβ3-targeted magnetic resonance contrast agent, PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2, for its ability to detect tumor angiogenesis and assess early response to antiangiogenic therapy using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Integrin αvβ3-positive U87 cells and control groups were incubated with fluorescein-labeled cRGD-conjugated dendrimer, and the cellular attachment of the dendrimer was observed. DCE MRI was performed on mice bearing KB xenograft tumors using either PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 or PEG-G3-(Gd-DTPA)6-(cRAD-DTPA)2. DCE MRI was also performed 2 hours after anti-integrin αvβ3 monoclonal antibody treatment and after bevacizumab treatment on days 3 and 6t. Using DCE MRI, the 30-minute contrast washout percentage was significantly lower in the cRGD-conjugate injection groups. The enhancement patterns were different between the two contrast injection groups. In the antiangiogenic therapy groups, a rapid increase in 30-minute contrast washout percentage was observed in both the LM609 and bevacizumab treatment groups, and this occurred before there was an observable decrease in tumor size. The integrin αvβ3 targeting ability of PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 in vitro and in vivo was demonstrated. The 30-minute contrast washout percentage is a useful parameter for examining tumor angiogenesis and for the early assessment of antiangiogenic treatment response.
authors.affiliation: Department of Radiology, Taipei City Hospital, Taipei.
authors.forename: Wei-Tsung
authors.initials: WT
authors.lastname: Chen
authors.forename: Tiffany Ting Fang
authors.initials: TT
authors.lastname: Shih
authors.forename: Ran-Chou
authors.initials: RC
authors.lastname: Chen
authors.forename: Shin-Yang
authors.initials: SY
authors.lastname: Tu
authors.forename: Wen-Yuen
authors.initials: WY
authors.lastname: Hsieh
authors.forename: Pang-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000068258:Bevacizumab; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003287:Contrast Media; D050091:Dendrimers / Q000138:chemical synthesis; D019786:Gadolinium DTPA / Q000138:chemical synthesis; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic; D011092:Polyethylene Glycols / Q000138:chemical synthesis; D034741:RNA, Small Interfering / Q000378:metabolism; D011877:Radionuclide Imaging; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D050091:Dendrimers; D039302:Integrin alphaVbeta3; D034741:RNA, Small Interfering; D000068258:Bevacizumab; D011092:Polyethylene Glycols; D019786:Gadolinium DTPA