# Magnetic Resonance Imaging Using a Chimeric Anti-Glypican-3 Antibody Conjugated with Gadolinium Selectively Detects Glypican-3-Positive Hepatocellular Carcinoma In Vitro and In Vivo

## TL;DR

A new MRI probe using a chimeric anti-GPC3 antibody with gadolinium can detect liver cancer in lab and animal models.

## Contribution

A novel chimeric anti-GPC3 antibody conjugated with gadolinium for selective MRI detection of GPC3-positive liver tumors.

## Key findings

- The ET58-DOTA-Gd probe selectively identified GPC3-positive tumors with good clarity.
- The probe showed low side effects in animal models and high specificity.
- It may serve as a non-invasive companion diagnostic for GPC3-targeted therapies.

## Abstract

Liver cancer is a typically fatal malignancy that is difficult to detect and treat early. A large percentage of liver cancer patients express a protein called glypican-3 (GPC3). Recent treatment approaches that specifically target GPC3 are being developed. To allow the identification of liver cancer patients that express GPC3, and to visualize the tumor size and locations, we developed a new diagnostic imaging probe by conjugating the standard magnetic resonance imaging (MRI) contrast agent to a highly specific chimeric anti-GPC3 antibody. In liver cancer cell lines and animal models, our GPC3-based MRI probe selectively identified GPC3-positive tumors with good clarity and low side effects. This probe may help identify liver cancer patients suitable for GPC3-targeted therapies and monitor their treatment response in a safe and non-invasive manner.

Background/Objectives: Glypican-3 (GPC3) is a cell surface oncofetal protein that is highly expressed in hepatocellular carcinoma (HCC) but absent in normal liver tissue, making it an attractive target for molecularly targeted diagnosis and therapy. To support GPC3-targeted treatment strategies, there is a need for a non-invasive imaging tool capable of detecting GPC3-positive tumors. Methods: We conjugated a commercially available murine anti-GPC3 antibody (1G12), or a proprietary chimeric anti-GPC3 antibody (ET58) to the standard magnetic resonance imaging (MRI) contrast agent, gadolinium, via a DOTA chelator. The resulting probes, 1G12-DOTA-Gd or ET58-DOTA-Gd, respectively, were assessed for in vitro relaxivity and binding specificity to GPC3-positive HCC cells, as well as for in vivo imaging performance in mouse xenograft models bearing GPC3-positive or GPC3-negative HCC tumors. Conclusions: ET58-DOTA-Gd shows high specificity, imaging efficacy, and a favorable immunogenicity profile, thereby making it a promising candidate for clinical translation as a GPC3-targeted MRI probe. It holds potential as a non-invasive companion diagnostic for identifying GPC3-positive HCC patients who may benefit from GPC3-targeted therapies.