Evaluation of Tumor Microvascular Response to Brivanib by Dynamic Contrast-Enhanced 7-T MRI in an Orthotopic Xenograft Model of Hepatocellular Carcinoma
Evaluation of Tumor Microvascular Response to Brivanib by Dynamic Contrast-Enhanced 7-T MRI in an Orthotopic Xenograft Model of Hepatocellular Carcinoma
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DOI：
10.2214/ajr.13.11042
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发表时间：
2014-06-01
影响因子：
5
通讯作者：
Lee, Won Jae
中科院分区：
文献类型：
--
作者：
Song, Kyoung Doo;Choi, Dongil;Lee, Won Jae
客观的。本文的目的是在人肝细胞癌 (HCC) 原位小鼠模型中使用动态对比增强 MRI (DCE-MRI) 评估布立尼布的抗血管生成作用。 材料和方法。对于人 HCC（HepG2 细胞系）原位裸鼠异种移植物，治疗组口服布立尼布，对照组给予赋形剂，持续 14 天。 DCE-MRI 在治疗开始前以及治疗开始后 7 天和 14 天进行。分析了治疗引起的肿瘤体积和微血管密度 (MVD) 的变化，通过 CD31 免疫组织化学评估。使用二室模型计算灌注参数，包括血浆和血管外细胞外间隙之间的体积传递常数（K-trans）、单位体积组织的血管外细胞外间隙分数（v（e））以及血管外细胞外间隙和血浆之间的速率常数（K-ep）。 结果。 Brivanib 在肿瘤体积中显示出有效的抗肿瘤活性。布立尼布治疗组的肿瘤平均（+/- SD）MVD（40.8 +/- 17.3 血管/视野）显着低于对照组（55.2 +/- 9.05 血管/视野）（p < 0.05）。在对照组中，K-trans 值在基线和治疗后 14 天之间显着增加 (p = 0.048)。在布立尼布治疗组中，K-trans 和 v(e) 值在基线和治疗后 7 天之间（分别为 p = 0.024 和 p = 0.031）以及在基线和治疗后 14 天之间（分别为 p = 0.043 和 p = 0.018）显着下降。基线和治疗后 14 天之间的 K-trans 和 v(e) 值之间的差异显示两组之间存在统计学显着差异（分别为 p = 0.004 和 p = 0.034）。 结论。 DCE-MRI 在人类 HCC 原位小鼠模型中是可行的，它可以无创监测布立尼布诱导的肿瘤微血管变化。
OBJECTIVE. The purpose of this article is to evaluate the antiangiogenic effects of brivanib using dynamic contrast-enhanced MRI (DCE-MRI) in an orthotopic mouse model of human hepatocellular carcinoma (HCC).MATERIALS AND METHODS. With human HCC (HepG2 cell line) orthotopic nude mouse xenografts, brivanib was administered orally to the treatment group, and the vehicle was administered to the control group for 14 days. DCE-MRI was performed before the start of the therapy and 7 and 14 days after the start of therapy. Treatment-induced changes in tumor volume and microvessel density (MVD) assessed by CD31 immunohistochemistry were analyzed. Perfusion parameters, including volume transfer constant between blood plasma and extravascular extracellular space (K-trans), fractional extravascular extracellular space per unit volume of tissue (v(e)), and rate constant between extravascular extracellular space and blood plasma (K-ep), were calculated using the two-compartment model.RESULTS. Brivanib shows potent antitumor activity in tumor volume. The mean (+/- SD) MVD of the tumors was statistically significantly lower in the brivanib-treated group (40.8 +/- 17.3 vessels/field) than in the control group (55.2 +/- 9.05 vessels/field) (p < 0.05). In the control group, the K-trans value increased statistically significantly between the baseline and 14 days after treatment (p = 0.048). In the brivanib-treated group, the K-trans and v(e) values decreased statistically significantly between baseline and 7 days after treatment (p = 0.024 and p = 0.031, respectively) and between baseline and 14 days after treatment (p = 0.043 and p = 0.018, respectively). The difference between the K-trans and v(e) values between baseline and 14 days after treatment showed a statistically significant difference between the two groups (p = 0.004 and p = 0.034, respectively).CONCLUSION. DCE-MRI is feasible in the orthotopic mouse model of human HCC, and it can noninvasively monitor brivanib-induced changes in tumor microvasculature.