整合素avβ3受体对比超声靶向造影评价喉癌血管生成的实验研究

血管生成是各种肿瘤赖以生存和侵袭的前提条件。发展新的、能准确无创并且可重复地评估肿瘤新生血管、预测肿瘤转移预后的影像技术手段，成为现代医学影像学的一个重要课题。我们的前期研究已经证实超声可清晰显示喉内的重要结抅，准确判断喉癌的发生位置、大小，可提供肿瘤的粘膜下、喉旁间隙及喉软骨侵犯等重要信息。本研究将以肿瘤新生血管内皮细胞特异性靶分子整合素avβ3为靶标制备靶向超声造影微泡，建立裸鼠人喉癌移植瘤动物模型，采用实时超声造影及时间-强度曲线定量分析技术评价该靶向超声造影剂显示喉癌肿瘤血流灌注特征的能力和效果，结合免疫组化检查方法探讨造影增强时间-强度曲线定量参数与肿瘤体积、VEGF表达、微血管密度的相关性，分析其与淋巴结转移及远处转移的相关关系，并进一步为以肿瘤血管生长因子内皮细胞为靶标的肿瘤分子成像研究及抗肿瘤血管生成的免疫和基因治疗奠定实验基础。

Angiogenesis, the recruitment of new blood vessels, occurs at a very early stage during the development and growth of different solid tumors. Targeted contrast-enhanced ultrasound imaging is increasingly being recognized as a powerful imaging tool for the detection and quanti?cation of tumor angiogenesis at the molecular level. Our preliminary studies have shown that the important structures of the larynx could be well visualized by high-frequency ultrasonography. Ultrasonography can provide adequate information with the location, size, intra- and extralaryngeal tissues extension, and laryngeal cartilages involvements of laryngeal carcinoma. In this project, we will combine the advantages of ultrasound with the advantages of molecular imaging through use of contrast-enhanced microbubbles targeted to Integrin avβ3, which has been shown to be over expressed in laryngeal carcinoma. In Aim 1 of this proposal, we will identify the Integrin avβ3-targeted microbubbles have a high specificity for binding to avβ3 expressing cells of laryngeal carcinoma. In Aim 2 we will test the accuracy of this targeted ultrasound imaging approach that allows detection of molecular alterations in tumor angiogenesis at different stage in subcutaneous cancer xenografts in mouse model. Molecular ultrasound imaging data will be quantitatively correlated with the expression of VEGF and micro vessel intensity obtained by immunohistochemical stains. The relationship between the parameters of time-intensity curve and the tumor size, status of lymph node, and metastasis will be also analyzed. In conclusion, the primary objective of this proposal is to identify and validate targeted microbubble contrast enhanced ultrasound for non-invasive, quantitative and objective evaluation tumor angiogenesis of laryngeal carcinoma. The successful completion of our aims will have the potential benefit to improve outcomes for patients with laryngeal cancer, and selecting and monitoring the response to anti-angiogenic therapy of laryngeal cancer.