MR monitoring of cyclooxygenase-2 inhibition of angiogenesis in a human breast cancer model in rats
MR monitoring of cyclooxygenase-2 inhibition of angiogenesis in a human breast cancer model in rats
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DOI：
10.1148/radiol.2431050658
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发表时间：
2007-04-01
期刊：
影响因子：
19.7
通讯作者：
Brasch, Robert C.
中科院分区：
文献类型：
--
作者：
Fournier, Laure S.;Novikov, Viktor;Brasch, Robert C.
目的：前瞻性评价大分子造影剂(MMCM)增强动态磁共振(MR)成像对环氧合酶-2(COX-2)抑制乳腺癌血管生成的影响。材料和方法：动物研究机构委员会批准该研究。将人乳腺癌细胞系MDA-MB-231植入30只纯合子雌性无菌大鼠体内，这些大鼠被交替分配到药物治疗组和对照组，前者每天服用塞来昔布7天，后者服用生理盐水。每只动物在静脉注射高分子造影剂后，分别在基线和给药24小时和7天后进行磁共振成像。每组中的11只大鼠成功地完成了所有三项研究，并拥有足够的技术质量的数据集。使用双向两室组织模型来估计每个肿瘤的内皮通透性(KPS)和血浆容量分数(FPV)。微血管密度也被测量，以使组织学评估血管生成。用重复测量方差分析和非配对双尾t检验分别评估同一组大鼠MR检查的平均值以及治疗组和对照组大鼠基础值之间的差异。结果：塞来昔布治疗7d后，MR成像检测的微血管KPS显著降低(P<；.05)，而对照组在7d后无明显变化。同样，微血管密度，作为血管生成的组织学指标，在治疗组显著低于对照组(P<；0.05)。结论：动态磁共振成像显示塞来昔布治疗后微血管对高分子量造影剂的通透性显著降低。
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 (KPS) 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 KPS 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.