寻找和研制性能优良的分子探针是分子影像学研究中的难点和技术瓶颈。本项目利用稀土上转换发光材料的高穿透性、光磁复合性、高化学稳定性等独特优点，针对前期研制的靶向细胞凋亡的小分子荧光探针穿透性差和生物背景干扰等不足，以稀土上转换纳米发光材料为信号组件，构建具有靶向凋亡的丹磺酰稀土上转换分子影像探针；利用我们建立的肿瘤细胞凋亡模型进行生物活性评价，明确适合于靶向成像的稀土上转换分子探针的结构；依托前期构建的整体动物模型和光学、磁共振成像技术平台，探索和比较不同结构的上转换分子探针在活体成像时的靶向性、特异性和敏感性，以期筛选出具有高灵敏度和特异性的分子影像探针；并开展深入的分子生物学研究，明确其靶向凋亡的作用机制。本项目是在我们已有研究工作基础上的延伸和深入，不仅将获得具有自主知识产权的靶向分子探针，而且将实现体内、体外利用同一分子探针对细胞凋亡的实时检测，并为活体凋亡成像提供敏感快速的新方法。

Molecular probes are the major driving force of molecular imaging science, providing many useful informations for the basic, preclinic and clinic research. Apoptosis (programmed cell death) plays a crucial role in the pathogenesis of many disorders, thus the detection of apoptotic cells can provide the physician with important information to further therapeutic strategies and would substantially advance patient care. Our previous work and other published results have demonstrated that dansyl probes can be used as imaging agents to specifically and selectively detect apoptotic cancer cells, but due to its limited light penetration depth associated with strong scattering for biological samples, the in vivo imaging are lack of high resolution. Rare-earth upconversion nanophosphors (UCNPs) show many attractive chemical and optical features, such as sharp emission lines, long lifetimes, superior photostability and no blinking. Such unique features are applied as the signal part for the design molecular probes by the conjugation of UCNPs and targets for both in vitro and in vivo imaging of apoptosis in this project. To further improve penetration depth and obtain higher targeted cell-specific probe for in vivo imaging, a series of UCNPs and targeted molecule (DNSBA derivatives and DNSBA-DEVD) are designed and synthesized as the potential probe for apoptosis imaging. The relationship between the structure of Dansyl-UNCPs from various approaches and related biological activities will be investigated using the established platform. After the biological activity screening, their specificities, sensitiveness and selectiveness of selected dansyl probes for in vivo imaging will be examed with the optical imaging and MRI in the apoptosis model in mice. Further mechanism experiments are explored to understand why and how the dansyl probe binds to apoptotic cancer cell. The rusults of this project will open an avenue for future in vivo experiments and for novel, self-renovation probes to detect apoptosis. It will also provide a new tool for apoptosis imaging with the same probe but for both in vitro and in vivo experiments.