# Pilot study of humanized glypican-3-targeted zirconium-89 immuno-positron emission tomography for hepatocellular carcinoma

## TL;DR

This study shows that a humanized antibody targeting GPC3 can effectively detect liver tumors in mice, offering a potential improvement in diagnosing hepatocellular carcinoma.

## Contribution

The study demonstrates the successful humanization of an anti-GPC3 antibody for immunoPET with no loss in tumor detection efficacy.

## Key findings

- Humanized αGPC3H maintained GPC3 binding in vitro and detected liver tumors in vivo.
- 89Zr-αGPC3H immunoPET showed high tumor uptake and tumor-to-liver ratios comparable to the murine version.
- The humanized antibody exhibited highly specific tumor targeting, making it a promising diagnostic tool for HCC.

## Abstract

Glypican-3 (GPC3)-targeted radioisotope immuno-positron emission tomography (immunoPET) may lead to earlier and more accurate diagnosis of hepatocellular carcinoma (HCC), thus facilitating curative treatment, decreasing early recurrence, and enhancing patient survival. We previously demonstrated reliable HCC detection using a zirconium-89-labeled murine anti-GPC3 antibody (89Zr-αGPC3M) for immunoPET. This study evaluated the efficacy of the humanized antibody successor (αGPC3H) to further clinical translation of a GPC3-based theranostic for HCC.

In vitro αGPC3 binding to HepG2 cells was assessed by flow cytometry. In vivo 89Zr-αGPC3H and 89Zr-αGPC3M tumor uptake was evaluated by PET/CT and biodistribution studies in an orthotopic xenograft mouse model of HCC.

αGPC3H maintained binding to GPC3 in vitro and 89Zr-αGPC3H immunoPET identified liver tumors in vivo. PET/CT and biodistribution analyses demonstrated high 89Zr-αGPC3H tumor uptake and tumor-to-liver ratios, with no difference between groups.

Humanized αGPC3 successfully targeted GPC3 in vitro and in vivo. 89Zr-αGPC3H immunoPET had comparable tumor detection to 89Zr-αGPC3M, with highly specific tumor uptake, making it a promising strategy to improve HCC detection.