^(125)I标记单抗用于MDA-MB-231荷瘤鼠中PD-L1表达的SPECT显像研究  

SPECT Imaging of PD-L1 Expression of MDA-MB-231 Tumor Xenograft Mice with ^(125)I-labeled Monoclonal Antibody

作　　者：何淑华[1,2] 汪洋 郑小北[1,2] 刘玉侠 贾丽娜[1] 张岚 HE Shuhua;WANG Yang;ZHENG Xiaobei;LIU Yuxia;JIA Lina;ZHANG Lan(Shanghai Institute of Applied Physics,Chinese Academy of Sciences,Shanghai 201800,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院上海应用物理研究所,上海201800 [2]中国科学院大学,北京100049

出　　处：《同位素》2024年第6期568-574,共7页Journal of Isotopes

摘　　要：为监测肿瘤中程序性死亡蛋白配体(PD-L1)的表达水平,本研究采用Iodogen法构建了靶向PD-L1的^(125)I-Atezolizumab。考察反应时间对标记率的影响,评价其在PBS和胎牛血清中的稳定性。研究^(125)I-Atezolizumab在大鼠体内的药时曲线,乳腺癌MDA-MB-231细胞和肿瘤模型中对PD-L1的靶向性。结果显示,室温反应5 min,^(125)I-Atezolizumab的标记率大于98%;^(125)I-Atezolizumab在PBS和胎牛血清中孵育48 h,放化纯度仍大于90%;^(125)I-Atezolizumab在大鼠体内的清除半衰期为(12.1±1.9)h。^(125)I-Atezolizumab免疫活性保持良好(IF=52%),乳腺癌细胞对其有特异性摄取;对MDA-MB-231荷瘤鼠的SPECT/CT显像结果显示,实验组肿瘤处具有较高的放射性摄取,对照组肿瘤对^(125)I-Atezolizumab的摄取可被Atezolizumab显著抑制,说明^(125)I-Atezolizumab与PD-L1靶点的结合具有特异性。初步研究结果表明,^(125)I-Atezolizumab标记方法简单高效、体外性质稳定,对PD-L1显像特异,具有用于肿瘤PD-L1表达水平监测的潜力,值得开展进一步研究。^(125)I-Atezolizumab was synthesized with Iodogen method for monitoring the expression level of PD-L1 in tumors.The influence of reaction time on ^(125)I-labeling efficiency and the stability of ^(125)I-Atezolizumab in PBS and fetal bovine serum were studied.The pharmacokinetics of ^(125)IAtezolizumab was evaluated in rats.Binding specificity to PD-L1 was determined using cellular uptake experiment of breast cancer cell line MDA-MB-231 in vitro and SPECT imaging of mice bearing MDA-MB-231 xenografts in vivo.The results indicated that the labeling yield of ^(125)IAtezolizumab was over 98% after 5 minutes reaction at room temperature.The radiochemical purity was more than 90% after 48 h incubation in PBS and fetal bovine serum.The elimination half-life of ^(125)I-Atezolizumab in rats was(12.1±1.9)h.The immunological activity of ^(125)I-Atezolizumab was well maintained(IF=52%)and high affinity was demonstrated in breast cancer cell line.SPECT/CT imaging of MDA-MB-231 tumor-bearing mice showed high radioactivity uptake in the tumor.Tumor uptake of ^(125)I-Atezolizumab was blocked in the presence of Atezolizumab,confirming target specificity.The preliminary results suggested that ^(125)I-Atezolizumab exhibited specificity for PD-L1 imaging using a simple and efficient labeling method,and demonstrated relatively good in vitro stability.It is potential to monitor the expression levels of PD-L1 in tumors by ^(125)I-Atezolizumab SPECT imaging and is worthy of further research.

关 键 词：程序性死亡蛋白配体1(PD-L1) ^(125)I标记 ^(125)I-Atezolizumab SPECT/CT 

分 类 号：TL923[核科学技术—核燃料循环与材料] R73-34[医药卫生—肿瘤]