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Visualization of Tumor Angiogenesis Using MR Imaging Contrast Agent Gd-DTPA-anti-VEGF Receptor 2 Antibody Conjugate in a Mouse Tumor Model

Jun, Hong Young    (Institute for Radiological Imaging Science, Wonkwang University School of Medicine, Jeonbuk 570-711, Korea.   ); Yin, Hong-Hua    (Institute for Radiological Imaging Science, Wonkwang University School of Medicine, Jeonbuk 570-711, Korea.   ); Kim, Sun-Hee    (Institute for Radiological Imaging Science, Wonkwang University School of Medicine, Jeonbuk 570-711, Korea.   ); Park, Seong Hoon    (Department of Radiology, Wonkwang University School of Medicine, Jeonbuk 570-711, Korea.   ); Kim, Hun Soo    (Department of Pathology, Wonkwang University School of Medicine, Jeonbuk 570-711, Korea.   ); Yoon, Kwon-Ha    (Institute for Radiological Imaging Science, Wonkwang University School of Medicine, Jeonbuk 570-711, Korea.  );
  • 초록

    Objective To visualize tumor angiogenesis using the MRI contrast agent, Gd-DTPA-anti-VEGF receptor 2 antibody conjugate, with a 4.7-Tesla MRI instrument in a mouse model. Materials and Methods We designed a tumor angiogenesis-targeting T1 contrast agent that was prepared by the bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and an anti-vascular endothelial growth factor receptor-2 (VEGFR2) antibody. The specific binding of the agent complex to cells that express VEGFR2 was examined in cultured murine endothelial cells (MS-1 cells) with a 4.7-Tesla magnetic resonance imaging scanner. Angiogenesis-specific T1 enhancement was imaged with the Gd-DTPA-anti-VEGFR2 antibody conjugate using a CT-26 adenocarcinoma tumor model in eight mice. As a control, the use of the Gd-DTPA-anti-rat immunoglobulin G (Gd-DTPA-anti-rat IgG) was imaged with a tumor model in eight mice. Statistical significance was assessed using the Mann-Whitney test. Tumor tissue was examined by immunohistochemical analysis. Results The Gd-DTPA-anti-VEGFR2 antibody conjugate showed predominant binding to cultured endothelial cells that expressed a high level of VEGFR2. Signal enhancement was approximately three-fold for in vivo T1-weighted MR imaging with the use of the Gd-DTPA-anti-VEGFR2 antibody conjugate as compared with the Gd-DTPA-rat IgG in the mouse tumor model ( p Conclusion MR imaging using the Gd-DTPA-anti-VEGFR2 antibody conjugate as a contrast agent is useful in visualizing noninvasively tumor angiogenesis in a murine tumor model.


  • 주제어

    Magnetic resonance (MR) contrast agent .   Molecular Imaging .   Angiogenesis .   Bioconjugation.  

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