Antiangiogenic Cancer Therapy: Monitoring with Molecular US and a Clinically Translatable Contrast Agent (BR55)
Antiangiogenic Cancer Therapy: Monitoring with Molecular US and a Clinically Translatable Contrast Agent (BR55)
复制标题
DOI：
10.1148/radiol.10091858
复制
发表时间：
2010-08-01
期刊：
影响因子：
19.7
通讯作者：
Willmann, Juergen K.
中科院分区：
文献类型：
--
作者：
Pysz, Marybeth A.;Foygel, Kira;Willmann, Juergen K.
目的：开发和测试人激酶插入结构域受体（KDR）靶向微泡（MB）（MBKDR），用于在分子水平上对KDR进行成像，并用于监测小鼠中人结肠癌异种移植肿瘤模型中的抗血管生成治疗。材料和方法：动物研究由实验动物护理机构管理小组批准。以低纳摩尔亲和力（KD = 0.5 nmol/L）结合人KDR的异二聚体肽偶联到含全氟丁烷的脂质壳MB（MBKDR）的表面上。在细胞培养物中，在流动剪切应力条件下（在100秒2 - 1）测试MBKDR对人KDR的结合特异性和与鼠血管内皮生长因子（VEGF）受体2（VEGFR 2）的交叉反应性。用40-MHz超声（US）换能器在小鼠中的人LS 174 T结肠癌异种移植物中测试MBKDR对VEGFR 2的体内结合特异性。使用MBKDR在6天内纵向测量有（n = 6）和无（n = 6）抗血管生成治疗（抗VEGF抗体）的肿瘤中靶向造影剂增强的US成像信号。进行离体VEGFR 2染色和微血管密度分析。显著性差异进行了评估（t，Mann-Whitney，或Wilcoxon测试）。结果：细胞培养实验显示MBKDR对人KDR的结合特异性和对小鼠VEGFR 2的交叉反应性（P 50%降低，P = 0.03）在治疗tumors.Conclusion：人MBKDR允许在体内成像和纵向监测人结肠癌异种移植物中VEGFR 2的表达。(C)RSNA，2010年
Purpose: To develop and test human kinase insert domain receptor (KDR)-targeted microbubbles (MBs) (MBKDR) for imaging KDR at the molecular level and for monitoring antiangiogenic therapy in a human colon cancer xenograft tumor model in mice.Materials and Methods: Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. A heterodimeric peptide that binds to human KDR with low nanomolar affinity (K-D = 0.5 nmol/L) was coupled onto the surface of perfluorobutane-containing lipid-shelled MBs (MBKDR). Binding specificity of MBKDR to human KDR and cross-reactivity with murine vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) were tested in cell culture under flow shear stress conditions (at 100 sec 2 1). In vivo binding specificity of MBKDR to VEGFR2 was tested in human LS174T colon cancer xenografts in mice with a 40-MHz ultrasonographic (US) transducer. Targeted contrast material-enhanced US imaging signal by using MBKDR was longitudinally measured during 6 days in tumors with (n = 6) and without (n = 6) antiangiogenic treatment (anti-VEGF antibody). Ex vivo VEGFR2 staining and microvessel density analysis were performed. Significant differences were evaluated (t, Mann-Whitney, or Wilcoxon test).Results: Cell culture experiments showed four times greater binding specificity of MBKDR to human KDR and cross-reactivity to murine VEGFR2 (P 50% lower, P = .03) in treated tumors.Conclusion: Human MBKDR allow in vivo imaging and longitudinal monitoring of VEGFR2 expression in human colon cancer xenografts. (C) RSNA, 2010