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血管内皮生长因子受体 2 特异性微泡用于大鼠模型中前列腺癌的分子超声检测。

Vascular endothelial growth factor receptor 2-specific microbubbles for molecular ultrasound detection of prostate cancer in a rat model.

机构信息

Department of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

出版信息

Invest Radiol. 2010 Oct;45(10):675-84. doi: 10.1097/RLI.0b013e3181efd6b2.

DOI:10.1097/RLI.0b013e3181efd6b2
PMID:20733504
Abstract

OBJECTIVES

To investigate whether rat prostate cancer can be detected by means of molecular ultrasound (US) using target-specific microbubbles versus a nonspecific contrast agent.

MATERIALS AND METHODS

A total of 20 Copenhagen rats were randomly examined 75 to 104 days after orthotopic implantation of G-Dunning rat prostatic tumor cells was using a high-end US system and either 1.2 mL/kg of the nonspecific agent A or 0.1 mL/kg of the target-specific agent B, containing vascular endothelial growth factor receptor 2 binding peptide. Contrast inflow (areas under the curve analysis) was determined during the first 30s, and all microbubbles were destroyed in the scan plane by means of the flash technique 20 minutes after intravenous administration to investigate specific accumulation of individual bubbles in tumors. Differences between normal prostate tissue and tumor were analyzed using luminance images. Sonographically determined tumor localization and extent were compared with magnetic resonance imaging and histology.

RESULTS

The median tumor size in the 20 rats determined on US (2.3 mm) and magnetic resonance imaging (2.4 mm) showed a very high correlation (r = 0.92, P = 0.01). Both agent A and agent B demonstrated higher vascularization of tumor periphery compared with normal prostate (P < 0.05) based on contrast inflow and areas under the curve analysis. Twenty minutes after administration, luminance for agent B in the tumor was significantly higher (P = 0.003) compared with nonspecific agent A (11.8-0.1). In consensus reading, the increase in signal intensity of the tumor compared with normal prostate tissue was significantly higher for agent B (P = 0.005), whereas no significant difference was found for agent A (P = 0.180).

CONCLUSIONS

The target-specific contrast agent was superior to the unspecific US contrast agent both with regard to early inflow analysis and specific accumulation in prostate cancer after 20 minutes.

摘要

目的

通过使用靶向特异性微泡与非特异性对比剂,研究分子超声(US)是否可检测大鼠前列腺癌。

材料与方法

共 20 只 Copenhagen 大鼠,在经直肠原位接种 G-Dunning 大鼠前列腺肿瘤细胞 75 至 104 天后,使用高端超声系统和 1.2ml/kg 的非特异性试剂 A 或 0.1ml/kg 的靶向特异性试剂 B(包含血管内皮生长因子受体 2 结合肽)进行随机检查。在最初 30 秒内进行对比剂流入(曲线下面积分析),并在静脉注射后 20 分钟内通过闪光技术破坏扫描平面中的所有微泡,以研究单个气泡在肿瘤中的特异性积聚。使用亮度图像分析正常前列腺组织和肿瘤之间的差异。通过超声确定的肿瘤定位和范围与磁共振成像和组织学进行比较。

结果

20 只大鼠的超声(2.3mm)和磁共振成像(2.4mm)确定的肿瘤中位数大小显示出非常高的相关性(r=0.92,P=0.01)。与正常前列腺相比,两种试剂 A 和试剂 B 均显示出肿瘤边缘更高的血管化(P<0.05),基于对比剂流入和曲线下面积分析。在给药 20 分钟后,肿瘤中试剂 B 的亮度明显高于非特异性试剂 A(P=0.003)(11.8-0.1)。在共识阅读中,与正常前列腺组织相比,肿瘤的信号强度增加,试剂 B 显著更高(P=0.005),而试剂 A 则无显著差异(P=0.180)。

结论

在早期流入分析和 20 分钟后在前列腺癌中的特异性积聚方面,靶向特异性对比剂优于非特异性 US 对比剂。

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