Immuno-PET imaging for non-invasive assessment of cetuximab accumulation in non-small cell lung cancer

Abstract

Abstract Backgrounds Overexpression of epidermal growth factor receptor (EGFR) has been established as a valid therapeutic target of non-small cell lung cancer (NSCLC). However, the clinical benefit of cetuximab as an EGFR-targeting drug is still controversial, partially due to the lack of effective means to identify suitable patients. This study aimed to investigate the potential of radiolabeled cetuximab as a non-invasive tool to predict cetuximab accumulation in NSCLC tumor xenografts with varying EGFR expression levels. Methods The NSCLC tumors in model mice were subjected to in vivo biodistribution study and positron emission tomography (PET) imaging 48 h after injection of either 111In- or 64Cu-labeled cetuximab. The EGFR expression levels of NSCLC tumors were determined by ex vivo immunoblotting. Results We found that tumors with high EGFR expression had significantly higher [111In]In-DOTA-cetuximab accumulation than tumors with moderate to low EGFR expression (P < 0.05). Strong correlations were found between [111In]In-DOTA-cetuximab tumor uptake and EGFR expression level (r = 0.893), and between [64Cu]Cu-DOTA-cetuximab tumor uptake with EGFR expression level (r = 0.915). PET imaging with [64Cu]Cu-DOTA-cetuximab allowed clear visualization of tumors. Conclusion Our findings suggest that this immuno-PET imaging can be clinically translated as a tool to predict cetuximab accumulation in NSCLC cancer patients prior to cetuximab therapy.

Keywords

• Immuno-PET
• Non-small cell lung cancer
• Cetuximab
• 64Cu
• Personalized medicine
• EGFR