Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany.
Invest Radiol. 2012 Jul;47(7):422-9. doi: 10.1097/RLI.0b013e31824f635a.
The aim of this study was to investigate the feasibility of using contrast-enhanced ultrasound (CEUS) in experimental breast cancer bone metastases and its utilization for assessment of early antiangiogenic treatment response in these lesions.
Nude rats bearing bone metastases (n = 20) were treated with the antiangiogenic tyrosine kinase inhibitor sunitinib daily from days 30 to 35 after MDA-MB-231 tumor cell inoculation (n = 10) and compared with sham-treated controls (n = 10). Imaging with ultrasound (US) and magnetic resonance imaging (MRI) was performed on days 30, 32, and 35 after tumor cell inoculation to determine tumor volume and parameters of vascularization in bone metastases. Contrast-enhanced US images were used to calculate wash-in and wash-out values, peak enhancement, and area under the curve from time intensity curves. In addition, a quantitative analysis software was used to determine regional blood volume and flow as well as filling times within bone metastases. For comparison, dynamic contrast-enhanced MRI provided amplitude A and exchange rate constant kep, respectively. Immunohistological analysis of the vasculature in bone metastases followed in vivo imaging experiments.
Although no changes in tumor volume were assessed in the observation time, significantly decreased values for peak enhancement, area under the curve, and wash-out were determined by CEUS in animals treated with sunitinib at day 35 after tumor cell inoculation. Analysis of CEUS images with quantitative analysis software showed significantly lower values for regional blood volume and regional blood flow as well as higher values for filling time in treated animals as early as 2 days after therapy onset. Dynamic contrast-enhanced MRI revealed significantly decreased values for parameter A at day 35 and kep at days 32 and 35 after tumor cell inoculation for treated animals. Immunohistology of bone metastases revealed significantly larger vessels and decreased positive area fraction for von Willebrand Factor in animals treated with sunitinib.
Contrast-enhanced US is feasible in experimental breast cancer bone metastases and depicts early antiangiogenic treatment response in advanced osteolytic lesions.
本研究旨在探讨超声造影（CEUS）在实验性乳腺癌骨转移中的可行性，并评估其在这些病变早期抗血管生成治疗反应中的应用。
将 MDA-MB-231 肿瘤细胞接种后 30 至 35 天（n = 10），每天给予抗血管生成酪氨酸激酶抑制剂舒尼替尼治疗，n = 10），并与假手术对照组（n = 10）进行比较。在肿瘤细胞接种后第 30、32 和 35 天进行超声（US）和磁共振成像（MRI）成像，以确定骨转移灶的肿瘤体积和血管化参数。使用 CEUS 图像计算血管内造影剂的流入和流出值、峰值增强、时间强度曲线下的曲线下面积。此外，还使用定量分析软件来确定骨转移灶内的局部血容量、血流和充盈时间。为了进行比较，动态对比增强 MRI 提供了幅度 A 和交换率常数 kep。在体内成像实验后，对骨转移灶中的血管进行免疫组织化学分析。
尽管在观察期间未评估肿瘤体积的变化，但在肿瘤细胞接种后第 35 天给予舒尼替尼治疗的动物中，CEUS 确定的峰值增强、曲线下面积和洗脱值显著降低。使用定量分析软件对 CEUS 图像进行分析显示，治疗后 2 天即可观察到局部血容量、局部血流降低，充盈时间升高。动态对比增强 MRI 显示，治疗后第 35 天的参数 A 以及第 32 和 35 天的 kep 值显著降低。骨转移灶的免疫组织化学显示，舒尼替尼治疗的动物中血管明显增大，von Willebrand 因子的阳性面积分数降低。
CEUS 可用于实验性乳腺癌骨转移，并可描绘晚期溶骨性病变中早期抗血管生成治疗反应。
