VEGFR2-Targeted Three-Dimensional Ultrasound Imaging Can Predict Responses to Antiangiogenic Therapy in Preclinical Models of Colon Cancer.
VEGFR2-Targeted Three-Dimensional Ultrasound Imaging Can Predict Responses to Antiangiogenic Therapy in Preclinical Models of Colon Cancer.
复制标题
DOI：
10.1158/0008-5472.can-15-3271
复制
发表时间：
2016-07-15
期刊：
影响因子：
11.2
通讯作者：
Willmann JK
中科院分区：
文献类型：
--
作者：
Zhou J;Wang H;Zhang H;Lutz AM;Tian L;Hristov D;Willmann JK
需要三维（3D）成像能力来评估抗癌治疗的反应，以最大限度地减少由于肿瘤的空间异质性而导致的二维方法常见的采样误差。近年来，由于临床3D矩阵阵列换能器的发展，使用靶向分子标记物的造影剂的3D超声分子成像（USMI）的可行性和可重复性大大提高。在这里，我们报告了临床前概念验证研究，表明VEGFR 2/KDR表达的3DUSMI准确地测量了对抗血管生成治疗的纵向治疗反应，在结肠癌的响应与非响应小鼠模型中。这些模型中的肿瘤在贝伐单抗血管生成治疗过程中表现出VEGFR 2靶向3DUSMI信号的差异模式。在有反应的肿瘤中，VEGFR 2信号在治疗开始后24小时就下降，而在无反应的肿瘤中，在任何时间点信号都没有变化。VEGFR 2信号的早期降低高度预测治疗结束时的治疗结果。我们的研究结果提供了一个临床前证据，证明3DUSMI可以预测抗血管生成治疗的反应，从而进一步研究其临床可转化性以预测患者的治疗结果。
Three-dimensional (3D) imaging capabilities to assess responses to anticancer therapies are needed to minimize sampling errors common to two-dimensional approaches as a result of spatial heterogeneity in tumors. Recently, the feasibility and reproducibility of 3D ultrasound molecular imaging (USMI) using contrast agents which target molecular markers has greatly improved, due to the development of clinical 3D matrix array transducers. Here we report preclinical proof of concept studies showing that 3DUSMI of VEGFR2/KDR expression accurately gauge longitudinal treatment responses to anti-angiogenesis therapy, in responding versus non-responding mouse models of colon cancer. Tumors in these models exhibited differential patterns of VEGFR2-targeted 3DUSMI signals during the course of anti-angiogenic treatment with bevacizumab. In responding tumors, the VEGFR2 signal decreased as soon as 24 hours after therapy was started, whereas in non-responding tumors there was no change in signal at any time point. The early decrease in VEGFR2 signal was highly predictive of treatment outcome at the end of therapy. Our results offer a preclinical proof that 3DUSMI can predict responses to anti-angiogenic therapy, warranting further investigation of its clinical translatability to predicting treatment outcomes in patients.