Annexin A5靶向造影剂介导的超声分子成像评价乳腺癌凋亡的新方法研究

项目名称： Annexin A5靶向造影剂介导的超声分子成像评价乳腺癌凋亡的新方法研究

项目编号： No.81201136

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 赵萍

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 已证实，凋亡通路受阻或凋亡机制缺失与乳腺肿瘤发病率高、预后差密切相关。明确凋亡状态对评价肿瘤靶向治疗效果、制定个体化治疗方案至关重要。目前，病理检测凋亡只适用于体外、磷脂结合蛋白（Annexin A5）的核医学及磁共振分子成像评价凋亡因成本高，对身体伤害大而浅尝辄止。Annexin A5分子的超声靶向成像为解决该难题提供了新方向。首先我们依据声动力学疗法（SDT）的剂量可控性优点，解决了凋亡诱导模型剂量难控制问题；再参照C.M.Lehr等方法将纳米粒子表面改性，然后与Annexin A5分子结合，进而解决了靶向造影剂制备的关键问题。本项目通过人为控制SDT治疗剂量来诱导鼠乳腺肿瘤不同程度凋亡，分别从体外细胞和活体动物水平来研究该靶向造影剂的特性、成像表现，分析其在凋亡诊断中的可行性，旨在探索该靶向造影剂活体内注射的最佳给药方式及凋亡定量监控方法，为临床肿瘤凋亡的超声分子诊断提供依据。

中文关键词： 纳米级超声造影剂；超声分子成像；肿瘤细胞凋亡；Annexin V分子；

英文摘要： It have confirmed that apoptosis pathway suppresion or deficiency is closely related to high incidence and poor prognosis of breast tumor. Clear apoptosis status is crucial to evalue targeted cancer therapy effect and set indiidualized treatment. At present, Pathology detection applies only to testing in vitro; evaluation apoptosis of nclear medicine and MRI image on Annexin A5 has not to study further because of high cost and much injures. Targeted ultrasound imaging on Annexin A5 provides new direction to solve this problem. First, we apply SDT self-control by people to solve the induction of apoptosis model dose difficult control problem. Next, we can modificate the nanoparticles surface to combind with Annexin A5 to prepare the Targeted Ultrasound Contrast Agent. In this study, we can control the SDT dose to induce cancer cell apoptosis at different levels. The features and imaging performance of the Contrast Agent will be researched in vitro and in vivo. Our goal is to explore a methd for best injection of the Contrast Agent and quantitative monitoring apoptosis and provide scientific basis for clinical tumor ultrasound molecular diagnosis of apoptosis.

英文关键词： Nanoscales ultrasound contrast agents；molecular ultrasound imaging；cell apoptosis of tumor；Annexin V；