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使用放射性标记的抗程序性死亡配体1单克隆抗体在免疫健全的三阴性乳腺癌小鼠模型中的放射免疫成像和靶向治疗

Radioimmunoimaging and targeting treatment in an immunocompetent murine model of triple-negative breast cancer using radiolabeled anti-programmed death-ligand 1 monoclonal antibody.

作者信息

Pang Xiaoxi, Liu Meng, Wang Rongfu, Liao Xuhe, Yan Ping, Zhang Chunli

机构信息

Department of Nuclear Medicine, Peking University First Hospital, Beijing, China.

出版信息

J Labelled Comp Radiopharm. 2018 Sep;61(11):826-836. doi: 10.1002/jlcr.3650. Epub 2018 Jul 4.

Abstract

The overall aim of this study was to evaluate whether iodine-131 radiolabeled monoclonal antibody (mAb) targeting programmed death-ligand 1 (PD-L1) can be used for imaging of PD-L1 expression noninvasively in vivo and playing synergistic effect combined with immunotherapy. Anti-PD-L1 mAb was radiolabeled with iodine-131 ( I-PD-L1 mAb) and was characterized in vitro. Biodistribution and imaging in vivo were performed periodically. Therapy study was conducted in triple-negative breast cancer-bearing BALB/c mice. As results, the labeling efficiencies of I-PD-L1 mAb reached 80% ± 3%, with radiochemical purity of 97% ± 1%. I-PD-L1 mAb preserved the capacity to bind living PD-L1-expressing cells specifically in vitro. Tumor radioactivity uptake of I-PD-L1 mAb was significantly higher than that of control groups. The xenografts were clearly imaged from 48 to 72 hours noninvasively after injection of I-PD-L1 mAb, while the xenografts were not imaged in control groups. Tumor growth was significantly inhibited, and median survival time was remarkably prolonged in combination therapy group compared with control groups. It was concluded that I-PD-L1 mAb can be a potential theranostic candidate for visualizing of PD-L1 expression noninvasively and performing synergistic therapy in carcinomas.

摘要

本研究的总体目标是评估碘-131放射性标记的靶向程序性死亡配体1(PD-L1)的单克隆抗体(mAb)是否可用于在体内无创成像PD-L1表达,并与免疫疗法发挥协同作用。抗PD-L1 mAb用碘-131进行放射性标记(I-PD-L1 mAb)并在体外进行表征。定期进行体内生物分布和成像。在携带三阴性乳腺癌的BALB/c小鼠中进行治疗研究。结果,I-PD-L1 mAb的标记效率达到80%±3%,放射化学纯度为97%±1%。I-PD-L1 mAb在体外保留了特异性结合表达活PD-L1细胞的能力。I-PD-L1 mAb的肿瘤放射性摄取明显高于对照组。注射I-PD-L1 mAb后48至72小时可无创清晰成像异种移植瘤,而对照组未成像异种移植瘤。联合治疗组与对照组相比,肿瘤生长明显受到抑制,中位生存时间显著延长。得出结论,I-PD-L1 mAb可能是一种潜在的诊疗候选物,用于无创可视化PD-L1表达并在癌症中进行协同治疗。

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