基于胰腺癌分子特征HIP/PAP和肿瘤趋化因子受体CXCR4的双靶点分子探针的合成与临床前研究

胰腺癌早期影像学诊断是提高胰腺癌手术切除率、提高生存率的关键因素之一。本研究围绕胰腺癌的特异性分子标记——胰腺相关蛋白HIP/PAP展开研究。在前期进行的以HIP/PAP为靶点的示踪剂——18F-FEL的细胞学和动物模型显像研究的基础上，经过分析前期研究中瓶颈所在以及可行的改进方法后，本研究拟结合胰腺癌分子标记HIP/PAP和肿瘤趋化因子受体CXCR4进行分子探针改造，设计了双靶点分子探针—68Ga-NOTA-3PFEL-CPCR4，并以此为基础进行示踪剂合成与标记、体外细胞学验证、动物模型在体影像学及生物分布研究，最终实现初步的临床转化，探索其在胰腺癌特异性诊断方面的价值。

Early PET imaging of pancreatic carcinoma is one of the crucial factor to improve the resection rate and enhance the survival rate. In this paper, based on the previous study of 18F-FEL, a PET tracer targeting HIP/PAP, including cytology and microPET study on small animals and after the analysis of bottleneck of previous study and its feasible improvement method. We designed a dual-targeting probe 68Ga-NOTA-3PFEL-CPCR4 containing the structure of FEL and CPCR4. CPCR4 is a probe targeting chemokine receptor CXCR4 that belongs the family of G-protein-coupled receptors and is a key player in the process of cancer metastasis. Further preclinical study including organic synthesis and radiolabeling of NOTA-3PFEL-CPCR4, cytology in vitro, microPET imaging of small animals and biodistribution study are needed before the preliminary translational clinical study for the diagnosis and exploration in the pancreatic cancer.