Magnetic resonance imaging in an experimental model of human ovarian cancer demonstrating altered microvascular permeability after inhibition of vascular endothelial growth factor.
OBJECTIVE
Magnetic resonance imaging enhanced with macromolecular contrast medium was used to monitor effects of angiogenesis inhibition on tumor microvascular permeability and ascites volume in an athymic rat model of human ovarian cancer.


METHODS
Groups of 6 athymic rats implanted intraperitoneally with SKOV-3, a human ovarian cancer cell line, were treated through a 14-day course with antibody to vascular endothelial growth factor or with saline solution for control animals. Dynamic magnetic resonance imaging was performed with a 92,000-d contrast agent, albumin-(gadolinium-diethylenetriaminepentaacetic acid)(30). Vascular permeability was estimated from dynamic enhancement data that were analyzed with a unidirectional 2-compartment kinetic model.


RESULTS
Animals treated with vascular endothelial growth factor antibody accumulated significantly smaller volumes of peritoneal ascites (P <.05) and showed significantly lower magnetic resonance imaging-assayed tumor microvascular permeabilities (P <.05) than did control animals.


CONCLUSIONS
Magnetic resonance imaging enhanced with a macromolecular contrast agent in an athymic rat model of human ovarian cancer treated with anti-vascular endothelial growth factor antibody can be used to measure a reduction in tumor microvascular permeability, corresponding to a reduction in ascites production.
Gossmann
A
A
Center for Pharmaceutical and Molecular Imaging, Department of Radiology, University of California San Francisco, San Francisco, CA 94143-0628, USA.
Helbich
T H
TH
Mesiano
S
S
Shames
D M
DM
Wendland
M F
MF
Roberts
T P
TP
Ferrara
N
N
Jaffe
R B
RB
Brasch
R C
RC
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001201:Ascites / Q000517:prevention & control; D002199:Capillary Permeability; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D008279:Magnetic Resonance Imaging; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000503:physiopathology*; D010532:Peritoneal Diseases / Q000517:prevention & control; D051381:Rats; D011923:Rats, Nude; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors