Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Preclinical Pharmacokinetics and Biodistribution of LR004, a Novel Antiepidermal Growth Factor Receptor Monoclonal Antibody

Ying Zheng
ORCID logo ,
Guifang Dou
ORCID logo ,
Shuchen Liu
,
Zhiyun Meng
,
Eric I. Tsao
,
Gang Yu
,
Xiaoxia Zhu
,
Ruolan Gu
,
Zhuona Wu
,
Yunbo Sun
,
Peng Han
,
Hui Gan
*
Version 1 : Received: 11 December 2023 / Approved: 11 December 2023 / Online: 12 December 2023 (05:11:26 CET)

A peer-reviewed article of this Preprint also exists.

Zheng, Y.; Dou, G.; Liu, S.; Meng, Z.; Tsao, E.I.; Yu, G.; Zhu, X.; Gu, R.; Wu, Z.; Sun, Y.; Han, P.; Gan, H. Preclinical Pharmacokinetics and Biodistribution of LR004, a Novel Antiepidermal Growth Factor Receptor Monoclonal Antibody. Molecules 2024, 29, 545. Zheng, Y.; Dou, G.; Liu, S.; Meng, Z.; Tsao, E.I.; Yu, G.; Zhu, X.; Gu, R.; Wu, Z.; Sun, Y.; Han, P.; Gan, H. Preclinical Pharmacokinetics and Biodistribution of LR004, a Novel Antiepidermal Growth Factor Receptor Monoclonal Antibody. Molecules 2024, 29, 545.

Abstract

LR004 is a novel chimeric (human/mouse) monoclonal antibody developed for the treatment of advanced colorectal carcinoma with detectable epidermal growth factor receptor (EGFR) expression. We aimed to investigate the preclinical pharmacokinetics (PK) and in vivo biodistribution of LR004. The PK profiles of LR004 were initially established in rhesus monkeys. Subsequently, 125I radionuclide-labeled LR004 was developed and its binding activity to the EGFR antigen were evaluated. Furthermore, the biodistribution, autoradiography, and NanoSPECT/CT of 125I-LR004 in xenograft mice bearing A431 tumors were examined. The PK data revealed a prolonged half-life and nonlinear PK characteristics of LR004 within the dose range of 6–54 mg/kg. The radiochemical purity of 125I-LR004 was approximately 98.54%, and iodination of LR004 did not affect its specific binding activity to the EGFR antigen. In a classical biodistribution study, 125I-LR004 exhibited higher uptake in highly perfused organs than in poorly perfused organs. Prolonged retention properties of 125I-LR004 in tumors were observed at 4 and 10 days. Autoradiography and NanoSPECT/CT confirmed the significant accumulation and sustained retention of 125I-LR004 at the tumor site in xenograft mice. These findings demonstrated the adequate tumor targeting capabilities of 125I-LR004 in EGFR-positive tumors, which may improve dosing strategies and future drug development.

Keywords

monoclonal antibody; EGFR; tumor-targeting; pharmacokinetics; radionuclide-based biodistribution; nanoSPECT/CT

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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