Integrin alpha(v)beta(3)-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
Resource
Mol. Imaging, 11(4), 286-300
Journal
Mol. Imaging
Journal Volume
11
Journal Issue
4
Pages
286-300
Date Issued
2012
Date
2012
Author(s)
Chen, Wei-Tsung
Shih, Tiffany Ting Fang
Chen, Ran-Chou
Tu, Shin-Yang
Wen-Yuen, Hsieh
Yang, Pang-Chyr
Abstract
The purpose of this study was to validate an integrin alpha(v)beta(3)-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 alpha(v)beta(3)-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 alpha(v)beta(3) 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 alpha(v)beta(3) 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.
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