肝癌的高死亡率通常与诊断较晚及缺乏有效的治疗方法有关。大量研究发现CD146在包括肝癌在内的多种肿瘤血管内皮细胞上高表达，可以促进新生血管形成、肿瘤生长及转移。我们前期使用I-125-Anti-CD146-mAb进行HepG2肝癌荷瘤小鼠SPECT/CT显像及放射免疫治疗，发现其在肿瘤具有高的浓集及生长抑制效应，但注射后早期血液及肝脏背景较高，因此，显像信噪比低，同时也会对骨髓以及其他正常器官产生高的非特异性辐射损伤。基于该抗体在肝癌组织具有高吸收和慢的药代动力学特性，通过肿瘤预定位策略将有效解决这一矛盾。本项目将采用生物正交点击化学方法，构建由反式-环辛烯（TCO）偶联的Anti-CD146-mAb和F-18/Re-188标记1,2,4,5-四嗪（Tz）组成的肿瘤预定位体系来提高肝癌PET显像及放射免疫治疗的靶向性，为实现肝癌“个体化、一体化”的诊疗模式进行临床前探索研究。

The poor prognosis of patients with hepatocellular carcinomas attributed to delaying diagnosis and lack of effective treatment. CD146 receptors were found over-expressed in varieties of tumor vascular endothelial including hepatocellular carcinomas, which can promote tumor growth, angiogenesis and metastasis. In our previous studies, I-125 labeled Anti-CD146-mAb was used for SPECT/CT imaging and RIT on mice bearing HepG2 tumors, it was found that this probe accumulated highly in tumor area, but blood and liver background was also high at early time points, which will reduce the imaging signal-to-noise ratios and produce high nonspecific radiation damage on bone marrow and other normal organs. According to our previous research and the properties of this antibody, we speculate that the pretargeting strategy can effectively resolve this conflict. Herein, this study will use the bioorthogonal click chemistry method to fabricate Anti-CD146-mAb coupling trans-cyclooctene (TCO) and F-18/Re-188 labeled 1,2,4,5-triazine (Tz) pretargeting system to improve the SNR of imaging and radioimmunotherapy, also reduce the normal tissue non-specific radiation injury. Therefore, this potential individual and integrated system will facilitate the accurate diagnosis of hepatocellular carcinomas, and screening suitable patients for RIT treatment.