喉癌血管生成拟态的超声分子影像研究

血管生成拟态(VM)是一种不依赖宿主血管内皮细胞的全新的微循环模式，与肿瘤的生长、转移及复发密切相关。如何利用影像学手段从分子水平阐明VM的潜在机制，成为现代医学影像学的重要课题。靶向超声分子显像目前已成功应用于肿瘤、动脉粥样硬化、炎症、血栓等多种疾病的早期诊断及病程监测，但迄今未见其用于评价喉癌血管生成拟态的报道，VM与喉癌浸润转移的内在联系仍不明确。我们的前期研究以“生物素 - 亲和素”体系成功制备出新型的能与血管内皮细胞特异性黏附的RGD靶向微泡造影剂。进一步地，将RGD靶向微泡用于移植瘤动物模型体内超声分子成像实验，结果显示超声分子显像可有效评价整合素 ανβ3在肿瘤血管新生中的表达。基于以上研究基础，本研究拟制备一种新型的靶向肿瘤血管生成拟态的基质金属蛋白酶-1微泡造影剂，建立不同生长阶段裸鼠人喉癌移植瘤动物模型，从超声分子影像学水平探讨VM形成与喉癌浸润转移的关系及潜在机制。

Vasculogenic Mimicry (VM), is a novel type of blood supplement involved in the development, metastasis and recurrence of the tumor. It was identified by the formation of a tubular, fracture-like structure by tumor cells but not endothelial cells. Targeted contrast-enhanced ultrasound imaging is increasingly being recognized as a powerful imaging strategy for the early detecting and monitoring tumor angiogenesis, atherosclerosis, inflammation, and thrombus at the molecular level. Our preliminary studies have constructed a RGD microbubbles (MBs) that can specifically binding to αvβ3 integrin-expressing cells via biotin-avidin linkage. Moreover, these RGD-MBs enable noninvasive in vivo visualization of changes in tumor angiogenesis during tumor growth in subcutaneous cancer xenografts. In this project, we propose preparation of a novel microbubbles targeted to vasculogenic mimicry, which has been shown to be expressing in laryngeal carcinoma. In Aim 1 of this proposal, we will identify the matrix metalloproteinases-1 (MMP -1)-targeted microbubbles have a high specificity for binding to VM over expressing cells of laryngeal carcinoma. In Aim 2, in different stage of human laryngeal carcinoma (Hep-2) xenografts, we will evaluate the role of VM in laryngeal carcinoma, as well as the correlation between VM and tumor metastasis, invasion, and recurrence by using targeted ultrasound molecular imaging.