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.
作者
刘葳豪
马欢
李飞泽
李鸿岩
兰图
廖家莉
秦芝
刘宁
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)
出处
《同位素》
CAS
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)。
