期刊
ULTRASOUND IN MEDICINE AND BIOLOGY
卷 41, 期 10, 页码 2765-2773出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2015.05.023
关键词
Ultrasound molecular imaging; Microbubbles; alpha v beta(3) integrin; iRGD; Tumor angiogenesis
资金
- National Key Basic Research Program of China (973 Program) [2015 CB755500, 2014 CB744502, 2013 CB733800]
- National Natural Science Foundation of China [81371563, 81360482, 11325420, 81401435, 61327001]
- National High Technology Research and Development Program of China (863 Program) [2014 AA020503]
The design and fabrication of targeted ultrasound contrast agents are key factors in the success of ultrasound molecular imaging applications. Here, we introduce a transformable alpha v beta(3) integrin-targeted microbubble (MB) by incorporation of iRGD-lipopeptides into the MB membrane for non-invasive ultrasound imaging of tumor angiogenesis. First, the iRGD-lipopeptides were synthesized by conjugating iRGD peptides to distearoyl-phosphatidylethanolamine-polyethylene glycol 2000-maleimide. The resulting iRGD-lipopeptides were used for fabrication of the iRGD-carrying alpha v beta(3) integrin-targeted MBs (iRGD-MBs). The binding specificity of iRGDMBs for endothelial cells was found to be significantly stronger than that of control MBs (p < 0.01) under in vitro static and dynamic conditions. The binding of iRGD-MBs on the endothelial cells was competed off by pre-incubation with the anti-alpha v or anti-beta(3) antibody (p < 0.01). Ultrasound images taken of mice bearing 4T1 breast tumors after intravenous injections of iRGD-MBs or control MBs revealed strong contrast enhancement within the tumors from iRGD-MBs but not from the control MBs; the mean acoustic signal intensity was 10.71 +/- 2.75 intensity units for iRGD-MBs versus 1.13 +/- 0.18 intensity units for the control MBs (p, 0.01). The presence of alpha v beta(3) integrin was confirmed by immunofluorescence staining. These data indicate that iRGD-MBs can be used as an ultrasound imaging probe for the non-invasive molecular imaging of tumor angiogenesis, and may have further implications for ultrasound image-guided tumor targeting drug delivery. (E-mail: lmeihong@fimmu.com or hr.zheng@siat.ac.cn) (C) 2015 World Federation for Ultrasound in Medicine & Biology.
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