Visualization of Tumor Angiogenesis Using MR Imaging Contrast Agent Gd-DTPA-anti-VEGF Receptor 2 Antibody Conjugate in a Mouse Tumor Model.
10.3348/kjr.2010.11.4.449
- Author:
Hong Young JUN
1
;
Hong Hua YIN
;
Sun Hee KIM
;
Seong Hoon PARK
;
Hun Soo KIM
;
Kwon Ha YOON
Author Information
1. Institute for Radiological Imaging Science, Wonkwang University School of Medicine, Jeonbuk 570-711, Korea. khy1646@wonkwang.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Magnetic resonance (MR) contrast agent;
Molecular Imaging;
Angiogenesis;
Bioconjugation
- MeSH:
Adenocarcinoma/*pathology;
Animals;
Colonic Neoplasms/*pathology;
Contrast Media/chemistry/*diagnostic use;
Gadolinium DTPA/chemistry/*diagnostic use;
Immunoenzyme Techniques;
Magnetic Resonance Imaging/*methods;
Mice;
Mice, Nude;
Neovascularization, Pathologic/*diagnosis;
Rats;
Statistics, Nonparametric;
Tumor Cells, Cultured;
Vascular Endothelial Growth Factor Receptor-2/*antagonists & inhibitors/chemistry
- From:Korean Journal of Radiology
2010;11(4):449-456
- CountryRepublic of Korea
- Language:English
-
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.
