Korean Journal of Radiology

The Korean Society of Radiology (대한영상의학회)
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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 Schoolof Medicine) ;
  • Yin, Hong-Hua (Institute for Radiological Imaging Science, Wonkwang University Schoolof Medicine) ;
  • Kim, Sun-Hee (Institute for Radiological Imaging Science, Wonkwang University Schoolof Medicine) ;
  • Park, Seong-Hoon (Department of Radiology, Wonkwang University School of Medicine) ;
  • Kim, Hun-Soo (Department of Pathology, Wonkwang University School of Medicine) ;
  • Yoon, Kwon-Ha (Institute for Radiological Imaging Science, Wonkwang University Schoolof Medicine)
  • Received : 2009.08.25
  • Accepted : 2010.02.22
  • Published : 2010.08.01
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Abstract

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 < 0.05). VEGFR2 expression in CT-26 tumor vessels was demonstrated using immunohistochemical staining. 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.

Keywords

References

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