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. 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.

Gadomer-17 in Contrast Enhanced MR Imaging of Reperfused Myocardial Infarction in a Cat Model

PURPOSE: To evaluate in reperfused myocardial infarction in a cat model, the time-course of signal enhancement as seen on Gadomer-17 enhanced MRI, and to correlate the size of the enhanced area with that of the infarct area as revealed by on histochemical examination. MATERIALS AND METHODS: Five cats which had undergone occlusion of the LAD followed by reperfusion underwent MR imaging. After T2-weighted imaging, Gadomer-17 enhanced T1-weighted images were obtained in four cats during a six-hour period, and in one during a three-hour period. Signal intensities were measured in the enhanced and non-enhanced areas of enhanced T1-weighted images. and using 2,3,5-triphenyl tetrazolium chloride (TTC) histochemical staining, the size of the abnormal signal area on each image was compared with that of the infarct area. RESULT: The enhanced area seen on enhanced T1-weighted images showed rapidly increased signal intensity following the administration of Gadomer-17. Maximum enhancement was detected during a 40 -60 minutes period, with an average enhancement of 168 +/-9.9% of normal myocardium. TTC staining revealed that the size of the high signal area on T2-weighted images and of the enhanced area on enhanced T1-weighted images was greater than that of the infarct area (p<0.05). CONCLUSION: In reperfused myocardial infarction in a cat model, Gadomer-17 enhanced MR imaging delineates both reversibly and irreversibly damaged myocardium, with strong enhancement and a broad temporal window. We may therefore expect that Gadomer-17 is useful for demonstrating myocardial injury.