Dynamic contrast-enhanced magnetic resonance imaging as a surrogate marker of tumor response to anti-angiogenic therapy in a xenograft model of glioblastoma multiforme

• Published in: Journal of magnetic resonance imaging Vol. 15; no. 3; pp. 233 - 240
• Main Authors: Gossmann, Axel, Helbich, Thomas H., Kuriyama, Nagato, Ostrowitzki, S., Roberts, Timothy P.L., Shames, David M., van Bruggen, N., Wendland, Michael F., Israel, Mark A., Brasch, Robert C.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01-03-2002
• Subjects: angiogenesis inhibition; Animals; Antibodies, Monoclonal - therapeutic use; Biomarkers, Tumor; Brain Neoplasms - blood supply; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Capillary Permeability; contrast enhanced; Contrast Media; Endothelial Growth Factors - immunology; Glioblastoma - blood supply; Glioblastoma - drug therapy; Glioblastoma - pathology; glioblastoma multiforme; Magnetic Resonance Imaging - methods; microvascular permeability; MRI; MRI, contrast enhanced; Rats; Rats, Nude; Tumor Cells, Cultured; tumor treatment monitoring; Xenograft Model Antitumor Assays
• ISSN: 1053-1807; 1522-2586
• DOI: 10.1002/jmri.10072

Purpose
To evaluate the effects of a neutralizing anti‐vascular endothelial growth factor (anti‐VEGF) antibody on tumor microvascular permeability, a proposed indicator of angiogenesis, and tumor growth in a rodent malignant glioma model.
Materials and Methods
A dynamic contrast‐enhanced magnetic resonance imaging (MRI) technique, permitting noninvasive in vivo and in situ assessment of potential therapeutic effects, was used to measure tumor microvascular characteristics and volumes. U‐87, a cell line derived from a human glioblastoma multiforme, was implanted orthotopically into brains of athymic homozygous nude rats.
Results
Treatment with the monoclonal antibody A4.6.1, specific for VEGF, significantly inhibited tumor microvascular permeability (6.1 ± 3.6 mL min–1100 cc–1), compared to the control, saline‐treated tumors (28.6 ± 8.6 mL min–1100 cc–1), and significantly suppressed tumor growth (P < .05).
Conclusion
Findings demonstrate that tumor vascular permeability and tumor growth can be inhibited by neutralization of endogenous VEGF and suggest that angiogenesis with the maintenance of endothelial hyperpermeability requires the presence of VEGF within the tissue microenvironment. Changes in tumor vessel permeability and tumor volumes as measured by contrast‐enhanced MRI provide an assay that could prove useful for clinical monitoring of anti‐angiogenic therapies in brain tumors. J. Magn. Reson. Imaging 2002;15:233–240. © 2002 Wiley‐Liss, Inc.