MR Monitoring of Cyclooxygenase-2 Inhibition of Angiogenesis in a Human Breast Cancer Model in Rats.
Purpose: 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. Materials and 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. Conclusion: Dynamic MR imaging revealed microvascular permeability to a high-molecular-weight contrast agent was significantly reduced by treatment with celecoxib. (c) RSNA, 2007.[1]References
- MR Monitoring of Cyclooxygenase-2 Inhibition of Angiogenesis in a Human Breast Cancer Model in Rats. Fournier, L.S., Novikov, V., Lucidi, V., Fu, Y., Miller, T., Floyd, E., Shames, D.M., Brasch, R.C. Radiology (2007) [Pubmed]
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