PNA介导可视化预靶向肿瘤的新型PRRT:177Lu-DOTA-PNA2/PNA1-EB-RGD

肿瘤多肽受体靶向放射性核素治疗（PRRT）是新型精准的肿瘤治疗方法，广谱受体靶向肽受限于在体循环时间短无法推广。白蛋白结合元件修饰可以增加靶向肽在体循环时间及肿瘤摄取水平。我们前期及既往研究发现经修饰的靶向肽注射后24小时，非靶器官的摄取水平才开始下降，因此，靶向肽在体循环时间增加的同时，正常组织器官的辐射暴露也随之增加。肽核酸（PNA）预靶向技术有望克服靶向肽在体循环时的辐射暴露，但PNA水溶性较差。白蛋白结合元件中伊文思蓝（EB）作为亲水性修饰可改善PNA的水溶性，与PNA预靶向技术在PRRT的应用中完美契合。基于前期PNA治疗及EB修饰靶向肽显像基础，本研究以靶向肽RGD为研究对象，使用EB对RGD、PNA进行修饰，构建可视化预靶向探针，通过互补PNA杂交实现探针在体放射性标记。证实PNA-EB模式预靶向技术应用于PRRT的可行性，为PRRT推广提供一种安全有效的新策略

Tumor peptide receptor radionuclide therapy (PRRT) is a new type of accurate and efficient tumor treatment. Broad-spectrum receptor targeting peptides are limited by the short circulation time in the body and cannot achieve clinical transformation. The modification of albumin binding element can increase the time of the polypeptide in systemic circulation and the level of tumor uptake. Our study and previous studies have found that the uptake level of non-target organs begins to decline 24 hours after the injection of the modified targeting peptide. Therefore, as the circulation time of the receptor targeting peptide increases in the body, the radiation exposure of normal tissues and organs also increases. Peptide nucleic acid (PNA) pretargeting technology is expected to overcome radiation exposure caused by increased systemic circulation time of targeted peptides, but PNA has poor water solubility. Evans Blue (EB) as an albumin binding element can improve the water solubility of PNA as a hydrophilic modification, which is a perfect fit for the application of PNA pretargeting technology in PRRT. Based on our previous research foundation of PNA therapy and EB modified targeting peptide imaging, this study took RGD as the research object and used the highly water-soluble albumin binding element EB to modify RGD and PNA to construct a visualized pretargeting probe. The in vivo radiolabeling of tumors is achieved by complementary PNA hybridization. Finally confirmed the feasibility and superiority of the PNA-EB model pretargeting technology applied to PRRT, providing a safe and effective new strategy for clinical transformation of PRRT.