iNGR-IBA-TCO / 90Y-Tz：基于IEDDA预靶向技术的白蛋白偶联肿瘤PRRT新策略

肿瘤多肽靶向内照射治疗（PRRT）是使用肿瘤靶向多肽搭载治疗性核素的肿瘤靶向治疗技术；但其临床推广受限于多肽在肿瘤中有限的摄取水平。白蛋白偶联策略是提升靶向多肽肿瘤摄取水平的有效方法，可将多肽的肿瘤摄取水平提升至16-46%。然而，文献和我们的前期研究表明，白蛋白偶联的多肽探针需24-72小时方可达摄取峰值，造成放射性滞留、衰变于血液循环而无法快速投送至肿瘤的新问题，降低治疗效果并增加血池脏器的辐射剂量。基于IEDDA点击化学反应的预靶向技术有望化解上述问题，极具临床应用前景。本研究拟采用白蛋白偶联元件IBA修饰的肿瘤靶向多肽iNGR为研究对象，使用IEDDA点击新技术对预靶向的iNGR-IBA探针进行90Y体内标记，比较该策略与传统白蛋白偶联PRRT策略的疗效及辐射剂量。验证IEDDA点击新技术应用于白蛋白偶联PRRT中的可行性及优越性，为PRRT的临床推广提供新备选方案。

Peptide Receptor Radionuclide Therapy (PRRT) is a novel targeted tumor therapy technology. However, its clinical promotion is limited by the limited uptake level of peptide in tumor. The albumin-binding strategy is an effective way to improve the level of targeted peptide uptake in tumor, which can increase the level of the peptide tumor uptake to 16-46%. However, previous literature and our research show that the albumin-binding peptide probe requires up to 24-72 hours to reach the uptake peak, causing new contradiction between prolonged blood circulation and rapid tumor radioactivity delivery, which reduces the treatment effect and increases the radiation dose of blood pool organ. The pretargeting technology based on IEDDA click chemical reaction is expected to dissolve the above contradiction and has a great potential for clinical application. In this study, we use the albumin-binder IBA modified tumor-targeting peptide iNGR as the research object. We used IEDDA click new technology to label the pretargeted iNGR-IBA probe in vivo, and compared the tumor therapeutic efficacy and radiation dose between this new strategy and the traditional albumin-binding strategy,in order to verify the feasibility and superiority of IEDDA based albumin-binding PRRT, and to provide a new alternative for the clinical application of PRRT.