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A Lipopeptide-Based αvβ₃ Integrin-Targeted Ultrasound Contrast Agent for Molecular Imaging of Tumor Angiogenesis.

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机构: [1]Department of Ultrasonography, Third Affiliated Hospital of Southern Medical University, Guangzhou, China [2]Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China [3]School of Life Science and Engineering, Southwest University of Science and Technology, Sichuan, Mianyang, China [4]Department of Echocardiography, Clinical Center of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, China [5]Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou, China [6]Department of Physics, University of Vermont, Burlington, Vermont, USA
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关键词: Ultrasound molecular imaging Microbubbles avb3 integrin iRGD Tumor angiogenesis

摘要:
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 αvβ3 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 distearoylphosphatidylethanolamine-polyethylene glycol 2000-maleimide. The resulting iRGD-lipopeptides were used for fabrication of the iRGD-carrying αvβ3 integrin-targeted MBs (iRGD-MBs). The binding specificity of iRGD-MBs 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-αv or anti-β3 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 αvβ3 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. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

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出版当年[2015]版:
大类 | 3 区 医学
小类 | 2 区 声学 3 区 核医学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 声学 3 区 核医学
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出版当年[2015]版:
Q1 ACOUSTICS Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
最新[2023]版:
Q2 ACOUSTICS Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

影响因子: 最新[2023版] 最新五年平均 出版当年[2015版] 出版当年五年平均 出版前一年[2014版] 出版后一年[2016版]

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第一作者机构: [1]Department of Ultrasonography, Third Affiliated Hospital of Southern Medical University, Guangzhou, China [2]Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
通讯作者:
通讯机构: [1]Department of Ultrasonography, Third Affiliated Hospital of Southern Medical University, Guangzhou, China [2]Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China [*1]Department of Ultrasonography, Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
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