海洋寡糖为载体的淋巴肿瘤早期检测造影剂及淋巴靶向药物的合成和新诊疗方法的动物研究

肿瘤转移是治疗失败的主要原因，而原发肿瘤相邻的淋巴结是转移的第一个站点。本课题针对前列腺癌高转移性的特点，提出了肿瘤转移淋巴结早期诊断和淋巴靶向给药新的诊疗方案，并合成淋巴检测试剂、淋巴靶向药物进行动物水平的基础研究，用于解决肿瘤治疗难题。本课题在前期的研究基础上，以海洋寡糖聚甘露糖醛酸为载体，合成淋巴专一性造影剂和淋巴靶向专一性药物，进行体外活性实验；建立新西兰大白兔VX2前列腺移植瘤模型及其淋巴转移模型，建立大鼠、裸鼠的人源前列腺癌模型；在兔VX2前列腺移植瘤模型进行淋巴转移的跟踪检测和淋巴转移早期诊断；在兔、大鼠和裸鼠上进行靶向抑制前列腺癌淋巴转移研究。课题在前列腺癌的淋巴肿瘤的的早期诊断检测、术前淋巴结显像准确确定肿瘤前哨淋巴结状况以及淋巴用药预防淋巴转移等方面有实用价值，将对肿瘤淋巴转移的预防、诊断和病情评估以及治疗有着重大意义。

Metastasis is one of the main reasons for death from cancer and Lymph nodes adjacent to the primary tumor are often the first site of metastases. For high metastatic prostate cancer, the aims of this project is new treatment program of lymph node metastasis early diagnosis and lymphatic targeted drug delivery. Based on our preliminary study, task of this project are 1) the synthesis of lymphoid-specific contrast agents and lymphatic targeting specific drugs used marine oligosaccharides poly-mannuronic acid as the carrier, and their in vitro activity test; 2) to establish New Zealand white rabbits VX2 prostate xenograft model and its lymphatic metastasis model, to establish human prostate cancer model of nude mice and SD mice, 3) racking and detection of lymph node metastasis in the rabbit VX2 prostate xenograft model and early diagnosis of lymph node metastasis; 4) the lymphatic targeting inhibition of prostate cancer lymph node metastasis research on the above rabbits, rats and nude mice models using marine oligosaccharides based lymphatic targeting specific drugs which we have synthesized. This project will make great efforts on basic research in the early diagnosis of prostate cancer lymphatic tumor detection, preoperative lymphoscintigraphy, accurately determination of tumor sentinel lymph nodes and drug prevention from lymph node metastasis.