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

  • N. Verlov,
  • O. Shashkova,
  • I. Krutetskaya,
  • L. Terekhina,
  • S. Shatik,
  • A. Pinevich,
  • V. Burdakov,
  • I. Kulakov,
  • T. Shtam,
  • A. Konevega,
  • A. Stanzhevskii,
  • M. Samoilovich

摘要

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.