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

## TL;DR

This study examines the pharmacokinetics and tumor targeting of LR004, a new antibody for treating colorectal cancer with EGFR expression.

## Contribution

The study introduces LR004 and demonstrates its tumor-targeting capabilities and nonlinear pharmacokinetics in preclinical models.

## Key findings

- LR004 shows prolonged half-life and nonlinear PK characteristics in rhesus monkeys.
- 125I-LR004 retains specific binding activity to EGFR and accumulates in highly perfused organs.
- NanoSPECT/CT and autoradiography confirm sustained tumor retention of 125I-LR004 in xenograft mice.

## 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 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 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.