Visualization of tumor angiogenesis using MR imaging contrast agent Gd-DTPA-anti-VEGF receptor 2 antibody conjugate in a mouse tumor model.
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.


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.


CONCLUSIONS
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.
Jun
Hong Young
HY
Institute for Radiological Imaging Science, Wonkwang University School of Medicine, Jeonbuk 570-711, Korea.
Yin
Hong-Hua
HH
Kim
Sun-Hee
SH
Park
Seong Hoon
SH
Kim
Hun Soo
HS
Yoon
Kwon-Ha
KH
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D003287:Contrast Media / Q000737:chemistry; D019786:Gadolinium DTPA / Q000737:chemistry; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D051381:Rats; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry
D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2; D019786:Gadolinium DTPA