基于比率型光声探针的肿瘤特征分子功能可视化及早期胃癌诊断研究

Gastric carcinoma (GC) is one of the main malignant tumors that seriously threaten human health. Precise diagnosis of early gastric cancer is the key for the treatment of GC. As one type of important tumor biomarkers, matrix metalloproteases (MMPs) have been widely used in early diagnosis and treatment of GC. Therefore, it is of great significance to achieve the functional visualization of MMPs in the process of tumor evolution in order to improve the diagnostic and therapeutic efficacy of GC in China. In this project, a number of smart molecular probes that are specifically responsive to MMPs will be rationally designed and synthesized. Next, we will explore their potential in functional visualization of MMPs using advanced medical imaging technologies such as near-infrared (NIR), single-photo emission computed tomography (SPECT), Magnetic resonance imaging(MRI) and photoacoustic imaging (PAI), and further reveal the mechanism of their roles in tumorigenesis, invasiveness, and metastasis of cancers, which may provide a valuable tool for tumor diagnosis. Additionally, the biological function and activity of MMPs in tumors can also be noninvasively and precisely visualized and quantified by the PA probe via the enzyme-dependent ratiometric PA signal ratios. By integrating the imaging techniques with in vitro diagnostic results and the pathological features, a new approach on the early diagnosis, metastasis warning and therapeutic evaluation of cancers will be developed. We thus envision that the successful completion of this project would bring a new insight for early diagnosis and precise treatment of clinical gastric cancer.

胃癌是威胁人类生命健康的主要恶性肿瘤之一，胃癌的早期精准诊断是提高胃癌治疗效果的关键。基质金属蛋白酶（MMPs）作为一类重要的肿瘤生物标志物被广泛地应用于胃癌的早期诊断与治疗研究。故开展MMPs在肿瘤演进过程中的功能可视化研究，对于提高我国胃癌诊疗水平意义重大。本项目拟构建一系列MMPs特异性识别并响应的胃癌智能化分子探针；利用探针对胃癌细胞的靶向性和对MMPs响应性，采用光学、SPECT、MRI和光声多模态成像技术，全方位、多角度获取MMPs在肿瘤发展过程中的功能信息，揭示其在肿瘤发生、发展和转移中的作用机制，建立一种基于肿瘤特征分子功能可视化的肿瘤诊断新方法；利用酶活依赖的比率型光声成像技术对肿瘤内MMPs进行无创、准确的功能定量分析，与体外检测信息和病理特征建立关联，发展一种准确可靠的肿瘤早期诊断、转移预警和疗效评估的可视化新方法，为临床胃癌的早期筛查与精准治疗提供新思路。

胃癌是威胁人类生命健康的主要恶性肿瘤之一，胃癌的早期精准诊断是提高胃癌治疗效果的关键。本项目围绕胃癌的早期诊断这一重要科学问题，以基质金属蛋白酶等重要肿瘤生物分子为研究对象，设计并构建了一系列肿瘤特异性识别并响应的多模态、多功能分子影像探针，结合先进的医学成像技术，实现了MMP-2/9、肿瘤微环境恶性因素（弱酸、ROS等）的活体高灵敏成像及功能可视化，并对这些关键生物分子在肿瘤演进过程中的重要功能和生物调控机制进行了系统性研究，成功发展了肿瘤关键生物分子特异响应型分子影像探针构筑的普适性新方法；进一步将肿瘤的体外诊断、病理分析与活体成像数据之间建立了准确关联，基于比率光声成像手段发展了生物分子在体定量可视化新方法，为肿瘤的早期诊断、转移预警、疗效评估和预后判定提供了新策略。通过本项目的实施与开展，获得一批高水平且拥有自主知识产权的研究成果，发表SCI论文15篇（I区论文14篇，II区论文1篇，影响因子＞8的论文14篇），均为第一标注。授权发明专利10项，申请发明专利10项（包括国际发明专利4项，中国发明专利6项）。