心肌细胞凋亡小分子探针PET显像研究

项目名称： 心肌细胞凋亡小分子探针PET显像研究

项目编号： No.81201116

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： 孙婷

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 持续的心肌细胞凋亡会导致有功能的心肌细胞大量丧失，与心力衰竭的发生发展密切相关。无创心肌细胞凋亡显像可以早期识别这些凋亡细胞，确定凋亡的部位和范围，有助于判断心肌损伤程度，评价抗凋亡治疗效果。目前的细胞凋亡显像剂难以实现快速清晰的心肌显像。我们以早期凋亡细胞的膜表面标志物磷脂酰丝氨酸（PS）为靶标，设计合成了新型氟标记小分子Zn2+-DPA类似物18F-FB-DPAZn2，用于心肌细胞凋亡PET显像研究，以实现心肌细胞凋亡的清晰显像。通过原代心肌细胞培养、心肌组织切片和建立心力衰竭大鼠模型，从细胞、组织和整体三个层次进行心肌细胞凋亡显像，对比免疫荧光、流式细胞仪、TUNEL、PET等不同检测方法的凋亡显像效果，评价心肌细胞凋亡PET显像的特异性和敏感性。可望将这种无创心肌细胞凋亡显像技术推广应用于临床。

中文关键词： DPA；心肌细胞；凋亡；PET；分子显像

英文摘要： Cardiomyocyte apoptosis is a continuous process which results in a large loss of functional cardiomyocytes and play a causal role in the development and progression of heart failure. The noninvasive imaging of cardiomyocyte apoptosis can detect the location and size of cardiomyocyte apoptosis in early stage and offer great benefit in determining the extent of myocardial damage and monitoring the anti-apoptotic therapies. Currently, there is no effective imaging agent used to detect cardiomyocyte apoptosis.Targeting the phosphatidylserine (PS) which is on the surface of dying cell, we designed and synthesized novel 18F labelled Zn2+-dipicolylamine(DPA) analogs 18F-FB-DPAZn2 for PET imaging of cardiomyocyte apoptosis in early stage, in order to get the clear pictures. We detect cardiomyocyte apoptosis in the levels of cell, tissue and animal by using primary cardiomyocyte culture, heart tissue alice and heart failure model. PET imaging of cardiomyocyte apoptosis is compared with other techniques, such as fluorescent imaging, flow cytometry and the terminal dUTP nick-end labeling (TUNEL) assay in vitro. Ultimately, we will assess the specificity and sensibility of the Zn2+-DPA analogs PET imaging, and make efforts to the utilization of noninvasive detection of cardiomyocyte apoptosis in clinical practice in the fut

英文关键词： dicipolylamine；cardiomyocyte；apoptosis；positron emission tomography；molecule imaging