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MR Monitoring of Cyclooxygenase-2 Inhibition of Angiogenesis in a Human Breast Cancer Model in Rats¹

¹ From the Center for Pharmaceutical and Molecular Imaging, University of California, San Francisco, San Francisco, Calif. Received April 20, 2005; revision requested June 15; final revision received February 28, 2006; accepted April 6; final version accepted August 1. Supported in part by National Institutes of Health grant no. RO1 CA82923. L.S.F. supported by a postdoctoral stipend from the Association pour la Recherche sur le Cancer (2001) and the Philippe Foundation (2002). Address correspondence to L.S.F., Department of Radiology, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France (e-mail: laure.fournier{at}gmail.com).

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.

© RSNA, 2007