靶向胰腺癌CD133+肿瘤干细胞多模态分子探针的构建及其在胰腺癌诊疗中的实验研究

The diagnosis of early stage pancreatic cancer is difficult, and its prognosis is poor. Seeking the early diagnostic method of pancreatic cancer may be the key approach to improve the prognosis, and the theory of the cancer stem cell put forward to bring new direction to the tumor diagnose and treatment.Our subject focus on the pancreatic tumor stem cells, we prepared multi-modal molecular imaging probe which by means of cancer stem cell surface specific marker as a target; rare earth upconversion luminescent materials, paramagnetic iron oxide, 188Re as imaging agent cover the three imaging of SPECT, MRI, and optical signal; we modificated the surface to make good bio-security and the ideal body distribution; and we use orthotropic tumor model to evaluate whether it can successfully targeting the CD133 + cancer stem cells; furthermore, we systematic review its value in pancreatic cancer treatment、tumor early diagnosis and neoplasm metastasis by the living, continuous, real time observation.The results of our project provide an important experimental base expected to clinical application, and also play a role in promoting the establishment of the tumor early diagnosis and non-invasive real-time evaluation of tumor treatment.

胰腺癌早期诊断困难、预后极差，寻求胰腺癌早期诊断方法可能是目前改善预后的关键，而肿瘤干细胞理论的提出给肿瘤诊断与治疗带来新的方向。本课题以胰腺癌干细胞为着眼点，以胰腺癌干细胞表面特异性标志物CD133为靶点，以稀土上转换发光纳米材料、顺磁氧化铁、188Re为显像剂，制备涵盖SPECT、MRI和光学三种成像信号的多模态分子影像探针；表面修饰使具有优良的生物安全性及理想的体内分布；以胰腺癌裸鼠原位移植瘤为模型，评价其是否可以成功靶向CD133+癌干细胞，并通过活体、连续、实时观察，系统研究其在胰腺癌早期诊断、转移监测以及肿瘤治疗方面的应用价值。本项目的研究结果有望为相关的临床应用提供重要的实验性研究基础，对于胰腺癌早期诊断方法的建立及无创实时评价胰腺癌治疗效果也可能起到一定的推动作用。

本课题首先进行了胰腺癌干细胞的分离、培养、纯化、鉴定；接着成功制备表面耦连抗单克隆抗体、内部包裹MTX、钆掺杂的NaYF4:Yb/Er复合稀土上转换发光纳米材料；最后，从体内外成像实验和体内外治疗两个水平，验证了这种复合稀土上转换发光纳米材料对胰腺癌干细胞的靶向和治疗作用。与国内外相关研究比较，本研究课题的特色是：提出并验证了一种全新的靶向及治疗肿瘤干细胞的多模态分子影像探针，系统研究其在成像诊断、疗效评估、转移监测、治疗等方面的价值，具有潜在的临床应用前景。