^(211)At及^(131)I标记尼妥珠单抗的荷瘤小鼠体内治疗研究  

Preliminary Treatment Study of ^(211)At and ^(131)I Labeled Nimotuzumab in Tumor-bearing Mice

作　　者：刘葳豪 马欢 李飞泽[1] 李鸿岩[2,3] 兰图 廖家莉 秦芝[2,3] 刘宁[1] 杨远友 LIU Weihao;MA Huan;LI Feize;LI Hongyan;LAN Tu;LIAO Jiali;QIN Zhi;LIU Ning;YANG Yuanyou(Key Laboratory of Radiation Physics and Technology of the Ministry of Education,Institute of Nuclear Science and Technology,Sichuan University,Chengdu 610064,China;Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou 730000,China;Gansu Provincial Isotope Laboratory,Lanzhou 730300,China)

机构地区：[1]四川大学原子核科学技术研究所辐射物理及技术教育部重点实验室,成都610064 [2]中国科学院近代物理研究所,兰州730300 [3]甘肃省同位素实验室,兰州730000

出　　处：《同位素》2022年第3期209-216,共8页Journal of Isotopes

基　　金：中央引导地方科技发展资金项目(甘财科2021-51号-11);中国博士后科学基金(2020M683309)。

摘　　要：以靶向表皮生长因子受体(EGFR)的尼妥株单抗(nimotuzumab)为载体,开展^(211)At和^(131)I一步法标记流程的建立和对荷U87MG胶质瘤裸鼠的初步治疗研究。结果表明,标记率约95%,在磷酸缓冲液(PBS)和10%胎牛血清(FBS)中能保持一定稳定性;瘤内注射24 h后,药物在肿瘤的放射性摄取率仍然能保持在(28.2±4.7)%ID·g^(-1)·^(131)I/^(211)At-ATE-nimotuzumab均可对U87MG实体瘤的生长产生明显的抑制作用,且呈剂量相关性;整个治疗过程中,药物对荷瘤鼠体重无明显影响并且有效地延长了生存时间;相较而言,20μCi的^(211)At-ATEnimotuzumab治疗组荷瘤小鼠中位生存时间长于200μCi ^(131)I-ATE-nimotuzumab治疗组荷瘤小鼠的中位生存期,分别为35 d和31.6 d。该工作进一步确定了α核素^(211)At在放射性靶向治疗研究中的潜力,为相关药物的临床前基础研究提供了重要参考。Using nimotuzumab targeting epidermal growth factor receptor(EGFR)as carrier,we have established a one-step labeling process for ^(211)At and ^(131)I and performed a preliminary treatment study on tumor-bearing mice.The labeling rate both were about 95%,and related radiolabeling complexes could maintain stability in PBS and FBS.The distribution showed that tumor uptake was still maintained to(28.2±4.7)%ID·g^(-1) after 24 h at intratumoral injection.The therapeutic effect of ^(131)I/^(211)At-ATE-nimotuzumab in U87MG glioma-bearing nude mice was further evaluated.The two labeled drugs can significantly inhibit the growth of solid tumors in a dose-dependent manner with no significant effect on the body weight of mice,effectively prolonging the survival time of subjects.In comparison,the median survival time of tumor-bearing mice in the ^(211)At-ATE-nimotuzumab group at 20μCi was longer than that in the ^(131)I-ATE-nimotuzumab group at 20μCi(35 days and 31.6 days).This work further confirmed that theα-nuclide ^(211)At has great potential in the research of radioactive targeted therapy,and can provide an important reference for the preclinical basic research of related drugs.

关 键 词：^(211)At ^(131)I 放射性靶向治疗 尼妥珠单抗 

分 类 号：TL923[核科学技术—核燃料循环与材料]