针对胃癌淋巴转移的上转换发光分子影像探针的构建及原位成像研究

Lymphatic metastasis is an important prognostic factor regarding long-term survival rate of gastric cancer (GC) patients. Pretreatment knowledge of lymph node (LN) status is extremely helpful for determining the prognosis and planning the optimal extent of lymphadenectomy. However, to date, no imaging modality has been demonstrated to be effective in detemination of LN metastasis status in GC. In this context, it is fundamentally meaningful to build up new imaging tools and methods for LN metastasis status evaluation in GC. Synergistically integration of paramagnetic/upconversion luminescence rare-earth nanoparticles have offered potential applications for dual-modality molecular imaging with both high-resolution and high-sensitivity. The present project is aiming at developing a new imaging technique based on the upconversion nanoprobes for lymphatic metastasis detection in GC. In detail, 1) fabrication of highly sensitive and specific nanoprobes based on the upconversion nanoparticles; 2) development of orthotropic lymphatic metastasis model of gastric cancer; 3) establishment of imaging method based on the upconversion nanoprobes for in vivo LN status evaluation and early detection of tiny LN metastasis. The major objective of this project is to develop methodology for constructing highly specific and sensitive molecular imaging probes suitable for the detection of lymphatic metastasis in GC.

淋巴转移是胃癌致死率高的关键原因，胃癌淋巴结转移的诊断评估决定着患者的治疗方案及预后。然而，系统性回顾分析表明，目前临床成像诊断方法尚难以对淋巴结转移实现准确分期。因此，亟须发展具有高灵敏及高分辨的成像方法用以实现胃癌淋巴结转移程度的评估。融合磁性/上转换发光的稀土纳米颗粒在高灵敏及高分辨的分子成像研究中均表现出广阔的发展空间，将有可能为解决胃癌淋巴转移的诊断评估提供新的手段。本项目围绕胃癌淋巴结转移诊断需求，拟以稀土上转换发光纳米颗粒为功能载体，开展胃癌淋巴转移特异性分子影像探针的构建研究，通过优化其晶体结构及表面修饰结构，得到具有高发光效率、良好生物相容性及肿瘤靶向特性的胃癌淋巴转移分子影像探针。结合合理的胃癌原位淋巴转移动物模型，深入研究胃癌淋巴转移的在体影像学评估方法，为未来指导先进功能的纳米探针在淋巴转移诊断中的应用奠定基础。

淋巴转移是胃癌致死率高的关键原因，胃癌淋巴结转移的诊断评估决定着患者的治疗方案及预后。然而，系统性回顾分析表明，目前临床成像诊断方法尚难以对淋巴结转移实现准确分期。因此，亟须发展具有高灵敏及高分辨的成像方法用以实现胃癌淋巴结转移程度的评估。融合磁性/上转换发光的稀土纳米颗粒在高灵敏及高分辨的分子成像研究中均表现出广阔的发展空间，将有可能为解决胃癌淋巴转移的诊断评估提供新的手段。本项目围绕胃癌淋巴结转移诊断需求，拟以稀土上转换发光纳米颗粒为功能载体，开展了胃癌淋巴转移特异性分子影像探针的构建研究，通过优化其晶体结构及表面修饰结构，得到了具有高发光效率、良好生物相容性及肿瘤靶向特性的胃癌淋巴转移分子影像探针。结合胃癌原位淋巴转移动物模型，研究胃癌淋巴转移的在体影像学评估方法，为未来指导先进功能的纳米探针在淋巴转移诊断中的应用奠定了坚实的基础。