Molecular and functional ultrasound imaging in differently aggressive breast cancer xenografts using two novel ultrasound contrast agents (BR55 and BR38)
Molecular and functional ultrasound imaging in differently aggressive breast cancer xenografts using two novel ultrasound contrast agents (BR55 and BR38)
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DOI：
10.1007/s00330-011-2138-y
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发表时间：
2011-09-01
影响因子：
5.9
通讯作者：
Palmowski, Moritz
中科院分区：
文献类型：
--
作者：
Bzyl, Jessica;Lederle, Wiltrud;Palmowski, Moritz
为了验证临床可翻译的长循环（BR 38）和VEGF 2靶向（BR 55）微泡（MB），并评估其区分不同侵袭性乳腺癌模型的能力，在健康小鼠中研究BR 38和BR 55的循环特性。使用BR 38测定MDA-MB-231（n = 5）或MCF-7（n = 6）肿瘤的相对血容量（rBV）。在相同的肿瘤中，测试了BR 55的体内结合特异性，并评估了VEGFR 2表达。数据验证包括定量免疫组织学分析。BR 38的血液半衰期比BR 55长（> 600 s vs. 218 s）。BR 38增强超声显示MDA-MB-231肿瘤中的血管化程度更高（p = 0.022），这与免疫组织学结果一致（p = 0.033）。体内竞争性结合实验证明了BR 55对VEGFR 2的特异性（p = 0.027）。BR 55的结合在MDA-MB-231中比在MCF-7肿瘤中显著更高（p = 0.049），这与组织学上发现的VEGFR 2水平相对应（p = 0.015）。然而，当将BR 55的水平标准化为rBV时，差异变得更小。BR 38和BR 55非常适合于表征和区分具有不同血管生成和侵袭性的乳腺癌。长循环BR 38 MB允许对较大或多个器官进行广泛的三维检查。BR 55的积累忠实地反映了肿瘤中VEGFR 2的状态，并描绘了血管生成的微小差异。
To characterise clinically translatable long-circulating (BR38) and VEGFR2-targeted (BR55) microbubbles (MB) and to assess their ability to discriminate breast cancer models with different aggressiveness.The circulation characteristics of BR38 and BR55 were investigated in healthy mice. The relative blood volume (rBV) of MDA-MB-231 (n = 5) or MCF-7 (n = 6) tumours was determined using BR38. In the same tumours in-vivo binding specificity of BR55 was tested and VEGFR2 expression assessed. Data validation included quantitative immunohistological analysis.BR38 had a longer blood half-life than BR55 (> 600 s vs. 218 s). BR38-enhanced ultrasound showed greater vascularisation in MDA-MB-231 tumours (p = 0.022), which was in line with immunohistology (p = 0.033). In-vivo competitive binding experiments proved the specificity of BR55 to VEGFR2 (p = 0.027). Binding of BR55 was significantly higher in MDA-MB-231 than in MCF-7 tumours (p = 0.049), which corresponded with the VEGFR2 levels found histologically (p = 0.015). However, differences became smaller when normalising the levels of BR55 to the rBV.BR38 and BR55 are well suited to characterising and distinguishing breast cancers with different angiogenesis and aggressiveness. Long-circulating BR38 MB allow extensive 3-dimensional examinations of larger or several organs. BR55 accumulation faithfully reflects the VEGFR2 status in tumours and depicts even small differences in angiogenesis.