^124I标记的抗程序性死亡蛋白配体-1单域抗体靶向肿瘤免疫显像的初步研究  

A preliminary study on targeting tumor imaging with 124I-labeled anti-programmed death ligand-1 single-domain antibody

作　　者：蒋金泉 张美欣 刘特立 徐晓霞 夏雷 朱华[1] 杨志[1] Jiang Jinquan;Zhang Meixin;Liu Teli;Xu Xiaoxia;Xia Lei;Zhu Hua;Yang Zhi(Department of Nuclear Medicine,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Peking University Cancer Hospital&Institute,Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处：《肿瘤综合治疗电子杂志》2020年第3期91-95,共5页Journal of Multidisciplinary Cancer Management(Electronic Version)

基　　金：国家自然科学基金(81401467,81671733);北大医学青年科技创新培育基金(BMU2018PY007)。

摘　　要：目的利用正电子核素^124I对人源化抗程序性死亡蛋白配体-1(programmed death ligand-1,PD-L1)的重链抗体的Fab段Nb1756进行标记并合成分子探针,通过系列基础实验评价该分子探针对于PD-L1检测的有效性和特异性。方法采用2-溴代丁二酰亚胺标记^124I,获得^124I-Nb1756分子探针并进行质量控制,分析其标记率、放射化学纯度和体内外稳定性。建立结肠癌LOVO荷瘤裸鼠模型,借助Micro-PET/CT设备,评价^124I-Nb1756在上述模型动物体内和肿瘤中的分布及代谢情况。结果^124I-Nb1756标记率>99%,放射化学纯度>99%,放射化学产率为75%~80%,比活度约为11.1 MBq/nmol。Micro-PET/CT显示该分子探针在肿瘤病灶中特异性摄取,肿瘤病灶中分子探针的聚集随着时间的延长而增加。结论^124I-Nb1756分子探针制备过程简便且标记率高,该分子探针能够特异靶向肿瘤病灶中的PD-L1,并可对肿瘤进行长时间显像观察,可为选择肿瘤治疗方案提供一定帮助。Objective To evaluate the effectiveness and specificity of the molecular probe for programmed death ligand-1(PD-L1)detection,we labeled the Fab Nb1756 of humanized anti-PD-L1 heavy chain antibody with positron radionuclide^124I and synthesize a molecular probe.Method^124I was labeled with 2-bromosuccinimide to obtain^124I-Nb1756 molecular probe and its quality control was carried out.The labeling rate,radiochemical purity and stability in vivo and in vitro were analyzed.The nude mouse model of colon cancer LOVO tumor was established,and the distribution/metabolism of^124I-Nb1756 in the above model animals were evaluated with Micro-PET/CT.Result The labeling rate of^124I-Nb1756 was>99%,the radiochemical purity was>99%,the radiochemical yield was 75%~80%,and the specific activity was about 11.1 MBq/nmol.The Micro-PET/CT showed that the molecular probe was specifically absorbed in tumor lesions,and with the extension of time,the aggregation of molecular probes in tumor lesions further increased.Conclusion The process of synthesis^124I-Nb1756 molecular probe is simple and with high labeling rate.The molecular probe can specifically target PD-L1 in tumor lesions,which is expected to provide some help to choose the treatment plan.

关 键 词：单域抗体 分子显像 碘-124 免疫显像 

分 类 号：R730.44[医药卫生—肿瘤]