用对比增强破坏-再灌注超声对不同剂量抗血管生成药物治疗后小鼠肿瘤血流的定量评估。

Quantitative assessment of tumor blood flow in mice after treatment with different doses of an antiangiogenic agent with contrast-enhanced destruction-replenishment US.

机构信息

Department of Ultrasound, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, 651 Dongfeng Road East, Guangzhou 510060, People's Republic of China.

出版信息

Radiology. 2011 May;259(2):406-13. doi: 10.1148/radiol.10101339. Epub 2011 Feb 3.

DOI:10.1148/radiol.10101339

PMID:21292869

Abstract

PURPOSE

To quantify tumor blood flow by using contrast material-enhanced destruction-replenishment ultrasonography (US) to evaluate tumor response to different doses of an agent for antiangiogenic treatment in hepatoma-bearing mice, with histologic measurements of microvascular density (MVD) as the reference standard.

MATERIALS AND METHODS

Experiments were approved by the regional animal care committee. Mice bearing subcutaneous H22 hepatoma were treated with different doses of thalidomide, 100 mg/kg in group B and 200 mg/kg in group C. Group A (control group) was treated with 0.5% carboxylmethylcellulose. Treatment groups and the control group included 10 mice each. Contrast-enhanced US was used to evaluate the percentage of nonenhanced area, and contrast-enhanced destruction-replenishment US was used to evaluate tumor blood flow. Tumor blood flow was compared with measurements of MVD. Comparisons were made by using one-way analysis of variance and the post hoc least significant difference test for multiple comparisons.

RESULTS

Contrast-enhanced gray-scale US showed significant increases in the percentage of nonenhanced area in group C (mean, 10.56% ± 7.25 [standard deviation]), as compared with groups A (mean, 2.40% ± 3.12; P = .004) and B (mean, 3.75% ± 5.55; P = .012). Contrast-enhanced destruction-replenishment US showed significant decreases of tumor blood flow in groups B and C, as compared with group A (P = .003 and P < .001, respectively), and the blood flow in group C was significantly lower than that of group B (P = .01). Immunohistochemical analysis revealed significant decreases of MVD in groups B and C, as compared with MVD in group A (P = .002 and P < .001, respectively); however, there was no significant difference in MVD between groups B and C (P = .21).

CONCLUSION

Quantification of tumor blood flow by using contrast-enhanced destruction-replenishment US shows the potential to guide drug dosage during antiangiogenic therapy.

摘要

目的

通过使用对比增强破坏-再灌注超声（US）定量肿瘤血流，评估荷肝癌小鼠接受不同剂量抗血管生成药物治疗的肿瘤反应，以微血管密度（MVD）的组织学测量作为参考标准。

材料与方法

实验得到了区域动物护理委员会的批准。荷皮下 H22 肝癌的小鼠分别接受不同剂量沙利度胺治疗，B 组 100mg/kg，C 组 200mg/kg，A 组（对照组）给予 0.5%羧甲基纤维素。每组 10 只小鼠，治疗组和对照组。使用对比增强灰度 US 评估无增强区域的百分比，使用对比增强破坏-再灌注 US 评估肿瘤血流。肿瘤血流与 MVD 测量进行比较。采用单因素方差分析和多重比较的事后最小显著差异检验进行比较。

结果

对比增强灰度 US 显示 C 组（平均 10.56%±7.25[标准差]）无增强区域百分比显著增加，与 A 组（平均 2.40%±3.12；P=0.004）和 B 组（平均 3.75%±5.55；P=0.012）相比。B 组和 C 组肿瘤血流的对比增强破坏-再灌注 US 显示明显降低，与 A 组相比（P=0.003 和 P<0.001），C 组的血流明显低于 B 组（P=0.01）。免疫组织化学分析显示 B 组和 C 组 MVD 明显降低，与 A 组相比（P=0.002 和 P<0.001）；然而，B 组和 C 组之间的 MVD 没有显著差异（P=0.21）。