基于FGFR受体靶向肿瘤分子影像探针的构建及应用基础研究

成纤维细胞生长因子受体（FGFR）可在多种肿瘤中表达，已成为肿瘤精准诊疗重要靶点之一。如何针对FGFR肿瘤受体靶点可视化指导肿瘤诊疗是临床分子影像的重要课题。本研究在前期研究经验的基础上，以NOTA为螯合剂，应用GAGG多肽为连接体，与FGFR靶向抑制剂AZD4547偶联，用18F标记，构建新型FGFR受体靶向PET分子影像探针，探索新型分子探针18F的标记率、靶向特性和稳定性，选用表达FGFR肺癌、结肠癌和不表达FGFR肺癌3种细胞和动物模型，研究18F标记的新型FGFR受体靶向分子探针(18F-NOTA-AZD4547）的细胞摄取与滞留情况、体内分布、体内显像和肿瘤特异摄取与FGFR表达相关性，开创肿瘤分子影像诊断新途径。本研究探索构建新型18F标记的FGFR受体靶向分子探针对FGFR高表达肿瘤靶向分子影像诊断，以及进一步肿瘤核素诊疗一体化策略和实践具有重要意义。

Fibroblast growth factor receptor (FGFR) can be expressed in a variety of tumors and has become one of the important targets for accurate diagnosis and treatment of tumors. In this study, based on our previous research experience, using NOTA as chelator, FGFR targeting inhibitor AZD4547 and GAGG poly-peptide were coupled together to construct a novel FGFR receptor targeting PET molecular probe labeling with 18F. To explore the novel molecular probe of 18F-NOTA-AZD4547 labeling rate, targeting characteristics and stability. Three different cellular and animal models of FGFR high expression lung cancer, colon cancer and lung cancer without FGFR expression were selected to study the cell uptake and retention of 18F receptor targeting molecular probes, in vivo distribution，tumor imaging and specific tumor uptake associated with FGFR expression, and to open a new path for tumor molecular imaging diagnosis. This study is important for FGFR hyperexpression tumor targeting molecular imaging diagnosis and further integration strategy and practice of radionuclide tumor diagnosis and treatment.