Molecular in vivo imaging of gastric cancer in a human-murine xenograft model: targeting epidermal growth factor receptor

Abstract

Background: The prognosis of gastric cancer depends on early diagnosis. Targeted therapies against epidermal growth factor receptors (EGFRs) are currently emerging for the treatment of gastric cancer.

Objective: To specifically visualize gastric cancer by using monoclonal antibodies targeting EGFR1 as molecular probes for in vivo molecular confocal laser endomicroscopy (mCLE) in a human-murine xenograft model.

Design: Prospective in vivo animal study.

Setting: Animal laboratory.

Interventions: Human gastric carcinoma xenografts were examined in 26 nude mice by using mCLE after injection of fluorescently labeled antibodies. Nine mice received low-dose anti-EGFR1 antibodies, 7 mice cetuximab, and 7 control mice isotype antibodies. Three mice were screened for autofluorescence without injection. Macroscopic fluorescence was evaluated in 2 additional mice.

Main outcome measurements: Molecular imaging of gastric cancer with confocal laser endomicroscopy.

Results: Fluorescence intensity in the anti-EGFR1 (P = .0145) and cetuximab group (P = .0047) was significantly higher than in isotype control mice. The same protocol allowed macroscopic fluorescence detection of tumor xenografts.

Limitations: Animal model.

Conclusions: In vivo microscopic and macroscopic molecular imaging of gastric cancer is feasible in a human-murine xenograft model with both diagnostic and therapeutic antibodies targeting EGFR1. In perspective, mCLE could help diagnose and molecularly characterize gastric cancer during ongoing gastroscopy and may even assist in the prediction of response to therapy.