Relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent and the level of VEGFR2 expression in an in vivo breast cancer model
Relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent and the level of VEGFR2 expression in an in vivo breast cancer model
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DOI：
10.7863/jum.2008.27.6.855
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发表时间：
2008-06-01
影响因子：
2.3
通讯作者：
Fleischer, Arthur C.
中科院分区：
文献类型：
--
作者：
Lee, Debbie J.;Lyshchik, Andrej;Fleischer, Arthur C.
目标。本研究的目的是表征血管内皮生长因子受体2 （VEGFR2）靶向超声造影剂（UCA）保留与乳腺癌肿瘤血管中VEGFR2表达之间的关系。方法：采用vegfr2靶向和非靶向uca以及高频超声系统对小鼠体内植入的67NR乳腺癌肿瘤进行评估。注射一剂UCA并循环4分钟，以使目标微泡结合。然后，对高功率超声破坏前后的2组图像进行序列处理。重新获得。测量破坏前和破坏后图像的平均视频强度，并将其用作肿瘤中UCA保留的相对度量。通过免疫组织化学染色定量测定VEGFR2表达水平和肿瘤血管密度，并与VEGFR2靶向UCA的保留量进行比较。结果。肿瘤中vegfr2靶向微泡的保留显著高于非靶向微泡的保留（平均+/- SD， 47.75 +/- 9.85 vs . 18.5 +/- 5.46 dB; P < .001）。研究发现，在所研究的肿瘤中，VEGFR2靶向UCA的保留与VEGFR2表达水平相关（r(2) = 0.41）。相反，非靶向UCA的保留与VEGFR2表达水平无关（r(2) = 0.08）。此外，vegfr2靶向UCA的保留与肿瘤血管的水平无关。结论。组织保留的VEGFR2靶向UCA分子超声信号的大小与VEGFR2表达相关。这些结果验证了分子超声技术在乳腺癌模型中用于体内检测和定量VEGFR2表达的可行性。
Objective. The aim of this study was to characterize the relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent (UCA) and VEGFR2 expression in tumor vasculature of breast cancer. Methods. 67NR breast cancer tumors implanted in mice were evaluated in vivo with both VEGFR2-targeted and nontargeted UCAs, and a high-frequency ultrasound system. A bolus of the UCA was injected and allowed to circulate for 4 minutes to allow binding of targeted microbubbles. After that, 2 sets of images before and after a high-power ultrasonic destruction sequence we. re acquired. The average video intensity of predestruction and postdestruction images was measured and used as 8 relative measure of retention of the UCA in the tumor. Levels of VEGFR2 expression and tumor vascular density were quantified by immunohistochemical staining and compared with retention of the VEGFR2-targeted UCA. Results. Retention of VEGFR2-targeted microbubbles in tumors was significantly higher than retention of nontargeted microbubbles (mean +/- SD, 47.75 +/- 9.85 versus 18.5 +/- 5.46 dB; P < .001). Retention of the VEGFR2-targeted UCA was found to correlate with the level of VEGFR2 expression in the studied tumors (r(2) = 0.41). In contrast, retention of the nontargeted UCA was not correlated with the level of VEGFR2 expression (r(2) = 0.08). Furthermore, retention of the VEGFR2-targeted UCA was not correlated with the level of tumor vascularity. Conclusions. The magnitude of the molecular ultrasonographic signal from a VEGFR2-targeted UCA retained by tissue correlates with VEGFR2 expression. These results validate the use of molecular, ultrasonography for in vivo detection and quantification of VEGFR2 expression in this breast cancer model.