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


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(-1)100 cc(-1)), compared to the control, saline-treated tumors (28.6 +/- 8.6 mL min(-1)100 cc(-1)), and significantly suppressed tumor growth (P <.05).


CONCLUSIONS
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.
Gossmann
Axel
A
Contrast Media Laboratory, Department of Radiology, University of California, San Francisco, California 94143-0628, USA.
Helbich
Thomas H
TH
Kuriyama
Nagato
N
Ostrowitzki
S
S
Roberts
Timothy P L
TP
Shames
David M
DM
van Bruggen
N
N
Wendland
Michael F
MF
Israel
Mark A
MA
Brasch
Robert C
RC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002199:Capillary Permeability; D003287:Contrast Media; D016228:Endothelial Growth Factors / Q000276:immunology*; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats; D011923:Rats, Nude; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D003287:Contrast Media; D016228:Endothelial Growth Factors