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. © 2025 Elsevier B.V., All rights reserved.