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

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

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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125I-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125I-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,125I-Atezolizumab的标记率大于 98%;125I-Atezolizumab在PBS和胎牛血清中孵育 48 h,放化纯度仍大于 90%;125I-Atezolizumab在大鼠体内的清除半衰期为(12。1±1。9)h。125I-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125I-Atezolizumab的摄取可被Atezolizumab显著抑制,说明125I-Atezolizumab与PD-L1靶点的结合具有特异性。初步研究结果表明,125I-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。
SPECT Imaging of PD-L1 Expression of MDA-MB-231 Tumor Xenograft Mice with 125I-labeled Monoclonal Antibody
125I-Atezolizumab was synthesized with Iodogen method for monitoring the expression level of PD-L1 in tumors.The influence of reaction time on 125I-labeling efficiency and the stability of 125I-Atezolizumab in PBS and fetal bovine serum were studied.The pharmacokinetics of 125I-Atezolizumab 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 125I-Atezolizumab 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 125I-Atezolizumab in rats was(12.1±1.9)h.The immunological activity of 125I-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 125I-Atezolizumab was blocked in the presence of Atezolizumab,confirming target specificity.The preliminary results suggested that 125I-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 125I-Atezolizumab SPECT imaging and is worthy of further research.

programmed death protein ligand 1(PD-L1)125I-labeling125I-AtezolizumabSPECT/CT

何淑华、汪洋、郑小北、刘玉侠、贾丽娜、张岚

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中国科学院上海应用物理研究所,上海 201800

中国科学院大学,北京 100049

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

2024

同位素
中国核学会同位素分会

同位素

CSTPCD
影响因子:0.405
ISSN:1000-7512
年,卷(期):2024.37(6)