Korean J Radiol.  2010 Aug;11(4):449-456. 10.3348/kjr.2010.11.4.449.

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

• Jun HY
• Yin HH
• Kim SH
• Park SH
• Kim HS
• Yoon KH

• KMID: 984899
• DOI: http://doi.org/10.3348/kjr.2010.11.4.449

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.

Keyword

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

MeSH Terms

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