MR monitoring of cyclooxygenase-2 inhibition of angiogenesis in a human breast cancer model in rats.
OBJECTIVE
To prospectively evaluate the ability of macromolecular contrast medium (MMCM)-enhanced dynamic magnetic resonance (MR) imaging to depict vascular changes in response to cyclooxygenase-2 (COX-2) inhibition of angiogenesis in a human breast cancer model.


METHODS
The institutional committee for animal research approved this study. A human breast cancer cell line, MDA-MB-231, was implanted in 30 female homozygotous athymic rats that were alternately assigned to either a drug treatment group that received celecoxib on a daily basis for 7 days or a control group that received saline. Each animal underwent MR imaging after intravenous administration of a high-molecular-weight contrast agent at baseline and again 24 hours and 7 days after administration. Eleven rats in each group successfully underwent all three studies and had data sets of sufficient technical quality. A bidirectional two-compartment tissue model was used to estimate transendothelial permeability (K(PS)) and fractional plasma volume (fPV) for each tumor. Microvessel density was also measured to enable histologic assessment of angiogenesis. Repeated-measures analysis of variance and unpaired two-tailed t tests were used to evaluate differences in mean values between MR examinations performed in the same rats and between baseline values in treated and control rats, respectively.


RESULTS
MR imaging-assayed microvascular K(PS) decreased significantly after 7 days of treatment with celecoxib (P < .05), but it was not significantly changed after 7 days in the control group. Likewise, microvascular density, a histologic surrogate of angiogenesis, was significantly (P < .05) lower in the treatment group than in the control group. The fPV did not significantly change in either group.


CONCLUSIONS
Dynamic MR imaging revealed microvascular permeability to a high-molecular-weight contrast agent was significantly reduced by treatment with celecoxib.
Fournier
Laure S
LS
Center for Pharmaceutical and Molecular Imaging, University of California, San Francisco, USA. laure.fournier@gmail.com
Novikov
Viktor
V
Lucidi
Vincenzo
V
Fu
Yanjun
Y
Miller
Theodore
T
Floyd
Eugenia
E
Shames
David M
DM
Brasch
Robert C
RC
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000378:metabolism; D000068579:Celecoxib; D045744:Cell Line, Tumor; D003287:Contrast Media; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011446:Prospective Studies; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D011923:Rats, Nude; D013449:Sulfonamides / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib