Comparison of Pharmacokinetic Parameters and Biodistribution of Full-Size Antibodies and Nanoantibodies Specific to Human PD-L1

IF 0.8 Q3 Engineering
N. Verlov, O. Shashkova, I. Krutetskaya, L. Terekhina, S. Shatik, A. Pinevich, V. Burdakov, I. Kulakov, T. Shtam, A. Konevega, A. Stanzhevskii, M. Samoilovich
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引用次数: 0

Abstract

The study of pharmacokinetic parameters and biodistribution of radiopharmaceuticals is the most important stage in the study of their effectiveness and safety for clinical usage. In the present work, a comparative study of 125I-labeled full-size therapeutic antibodies to human PD-L1 and recombinant single-domain heavy-chain antibodies (VHH) specific to the same biomarker was conducted. A mouse model of the tumor process induced by transplantation of CT26-PD-L1 recombinant cells stably expressing human PD-L1 receptor on their surface was used. The half-life time for VHH was almost 10 times shorter than for full-size antibodies while both pharmaceuticals demonstrated the ability of specific accumulation in CT26-PD-L1 tumor. The route of excretion for both drugs was mainly through urine. An abnormally rapid decrease of VHH concentration in the blood of mice was noted at the first 5 min after the radioconjugate administration.

Abstract Image

人PD-L1抗体与纳米抗体的药动学参数及生物分布比较
放射性药物的药代动力学参数和生物分布的研究是研究其临床使用有效性和安全性的重要环节。在本研究中,对125i标记的人PD-L1全尺寸治疗性抗体和针对同一生物标志物的重组单域重链抗体(VHH)进行了比较研究。采用表面稳定表达人PD-L1受体的CT26-PD-L1重组细胞移植诱导小鼠肿瘤模型。VHH的半衰期几乎比全尺寸抗体短10倍,而两种药物都显示出在CT26-PD-L1肿瘤中特异性积累的能力。两种药物的排泄途径均以尿液为主。在给药后的前5分钟,小鼠血液中VHH浓度异常迅速下降。
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来源期刊
Nanotechnologies in Russia
Nanotechnologies in Russia NANOSCIENCE & NANOTECHNOLOGY-
CiteScore
1.20
自引率
0.00%
发文量
0
期刊介绍: Nanobiotechnology Reports publishes interdisciplinary research articles on fundamental aspects of the structure and properties of nanoscale objects and nanomaterials, polymeric and bioorganic molecules, and supramolecular and biohybrid complexes, as well as articles that discuss technologies for their preparation and processing, and practical implementation of products, devices, and nature-like systems based on them. The journal publishes original articles and reviews that meet the highest scientific quality standards in the following areas of science and technology studies: self-organizing structures and nanoassemblies; nanostructures, including nanotubes; functional and structural nanomaterials; polymeric, bioorganic, and hybrid nanomaterials; devices and products based on nanomaterials and nanotechnology; nanobiology and genetics, and omics technologies; nanobiomedicine and nanopharmaceutics; nanoelectronics and neuromorphic computing systems; neurocognitive systems and technologies; nanophotonics; natural science methods in a study of cultural heritage items; metrology, standardization, and monitoring in nanotechnology.
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