PET/MR诊疗一体化靶向VEGFR-3/PD-L1分子探针相关结直肠癌及淋巴结转移的研究

Colorectal cancer (CRC) is the third most common cancer globally. Nearly half of the patient has reached stage T3-4 or with regional lymph node (LN) metastasis when in treatment. Preoperative knowledge LN metastasis can provide valuable information for determining the need for adjuvant therapy and the adequacy of surgical resection. Accurate identification of lymph node (LN) involvement in patients with CRC is crucial for prognosis and treatment strategy decisions. PET/MR has complementary advantages with PET and MRI, it plays a revolutionary role in the clinical diagnosis and treatment of various diseases. Vascular epidermal growth factor receptor 3 (VEGFR-3) is high expressed in tumor metastatic lymph nodes lymph angiogenesis. The clinical efficacy of PD-1/PD-L1 highly expressed in CRC patients. In this study, we based on the liposome targeting carrier, targeted VEGFR-3 or PD-L1, and entrap cetuximab. The physical and chemical properties of the multifunctional probe were characterized. Then the selective diagnosis ability with PET/MR and combination of molecular targeted, the immunotherapy and chemotherapy will be studied in the CRC and LN metastasis mouse models.

结直肠癌（CRC）是世界第三大常见肿瘤，近半数患者就诊时已达T3-4期或有区域淋巴结转移。早期诊断及判断有无淋巴结转移对CRC患者的治疗及预后有重要意义.如何在术前较准确的判断淋巴结转移是当前CRC临床中遇到的挑战性问题。一体化PET/MR扫描仪对临床多种疾病的诊断和治疗计划的制定起到革命性的推动作用。血管内皮生长因子受体-3（VEGFR-3）在肿瘤激活的新生淋巴管内皮特异性表达。针对PD-1及其配体PD-L1高表达CRC患者免疫治疗中PD-L1的表达情况及肿瘤微环境表达PD-L1与其抗体治疗的临床疗效相关。因此本项目拟以VEGFR-3/PD-L1为靶点，包裹西妥昔单抗，合成具有靶向诊疗多功能探针并表征其理化性质，在荷瘤鼠模型中PET/MR双模态成像研究其活体靶向分子成像机制，并探索利用分子靶向联合免疫治疗提高CRC的治疗效果。

结直肠癌（CRC）是世界第三大常见肿瘤，近半数患者就诊时已达T3-4期或有区域淋巴结转移。早期诊断及判断有无淋巴结转移对CRC患者的治疗及预后有重要意义.如何在术前较准确的判断淋巴结转移是当前CRC 临床中遇到的挑战性问题。一体化PET/MR扫描仪对临床多种疾病的诊断和治疗计划的制定起到革命性的推动作用。本项目最终构建并验证结直肠癌诊疗一体化探针2个：PD-L1适配体-金属有机框架-奥沙利铂探针用于结直肠癌的化疗-光动力治疗联合免疫治疗和Caspase3敏感的MPI及荧光双成像探针用于同时指示DC疫苗迁徙和死活状态以指导制定化疗联合活性DC疫苗治疗结直肠肿瘤的方案， 相关研究已发表 SCI 论著2篇，另有 1 篇 SCI 论著待投稿，1 篇已投稿会议摘要，相关研究成果已提交专利申请 2 项。该项目培养青年科研骨干 2 人，新晋升高级职称 1 人，博士研究生 2 人，硕士研究生 1 人。该研究成果具有重要的临床转化意义，能为提高我国结直肠癌患者的生存率和降低死亡率提供科学依据。该项目组多次派团队成员参与国际及国内知名学术会议，加深了团队与国际的学术交流，提高了我国学者在国际上的影响力。