活化的胰腺星状细胞（PSCs）是胰腺癌间质中最重要的细胞成分，靶向PSCs是胰腺癌诊疗研究的新思路。整合素α5（ITGA5）与α11（ITGA11）在胰腺癌间质中特异性高表达，主要由活化的PSCs合成分泌。本项目利用“诊疗核素组合”68Ga/177Lu标记由ITGA5与ITGA11的抑制剂融合而成的异源二聚化多肽，合成双靶点分子探针68Ga/177Lu-AV3-AXI。在裸鼠胰腺癌皮下、原位移植瘤（癌细胞与PSCs共注射建立）和PDX模型，验证双靶点分子探针较单靶点探针的PET显像优势；利用68Ga-AV3-AXI PET/CT显像监测、评估177Lu-AV3-AXI对肿瘤的治疗效果，结合肿瘤生长、动物存活时间及病理结果，明确双靶点分子探针通过靶向PSCs用于胰腺癌诊疗一体化的价值。项目基于靶向肿瘤间质成分，以“双靶点策略”尝试克服肿瘤异质性，有望为提高胰腺癌诊疗效果提供新的研究借鉴。

The activated pancreatic stellate cells (PSCs) are the most important cell components of pancreatic cancer stroma, and targeting PSCs is a new strategy for the diagnosis and therapy of pancreatic cancer. Integrin α5 (ITGA5) and Integrin α11 (ITGA11), which are synthesized and secreted mainly by the activated PSCs, are specifically overexpressed in pancreatic cancer stroma. In this project, the heterodimeric peptide AV3-AXI, which contains both ITGA5 inhibitor AV3 and ITGA11 inhibitor AXI, will be radiolabeled with the radio-theranostic pair 68Ga and 177Lu to develop the dual-targets molecular probe 68Ga/177Lu-AV3-AXI. The xenograft subcutaneous and orthotopic pancreatic cancer model will be established via the co-injection of pancreatic cancer cells and PSCs in nude mice, and pancreatic cancer patient-derived xenograft (PDX) mice model also will be established. The advantages of the dual-targets molecular probe 68Ga-AV3-AXI compared with the single-target molecular probe (68Ga-DOTA-AV3 and 68Ga-DOTA-AXI) for PET imaging of pancreatic cancer xenografts will be assessed. Further, 68Ga-AV3-AXI PET/CT imaging will be used to monitor and evaluate the therapeutic effect of 177Lu-AV3-AXI on the transplanted tumors, and the value of 68Ga/177Lu-AV3-AXI as the theranostics agent for the targeted imaging and therapy of pancreatic cancer will be confirmed according to the results from the tumor growth speed, the survival time of nude mice bearing tumor and the pathological study. Based on the idea of targeting the stromal components and further overcoming the tumor heterogeneity through a dual-targets strategy, the project is expected to provide new research reference for improving pancreatic cancer theranostic.