Abstract
BackgroundsOverexpression 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.MethodsThe 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.ResultsWe 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.ConclusionOur 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.
Highlights
Non-small cell lung cancer (NSCLC) remains a deadly cancer worldwide, even with advances in treatment strategies such as molecular targeted therapy and immunotherapy [1]
epidermal growth factor receptor (EGFR) expression in NSCLC cell lines Immunoblot analysis of the xenograft tumors showed that the eight NSCLC cell lines express various levels of EGFR (Fig. 1)
This study demonstrated the association between NSCLC tumor uptake of radiolabeled cetuximab and EGFR protein expression levels in a xenograft mouse model
Summary
Non-small cell lung cancer (NSCLC) remains a deadly cancer worldwide, even with advances in treatment strategies such as molecular targeted therapy and immunotherapy [1]. Studies suggest that strong overexpression of EGFR rather than other factors including KRAS mutation status is a determinant factor for the treatment efficacy of cetuximab in NSCLC patients. It is still unclear whether positivity in immunohistochemistry (IHC) or Fluorescent in situ Hybridisation (FISH) score. Yamaguchi et al BMC Cancer (2019) 19:1000 and/or squamous histology can be reliably predictive, presumably due to the heterogeneity of EGFR expression within tumors and/or limitations related to biopsy-based assessment such as limited tissue sampling [6, 7] Another approach that could assess EGFR status within the entire tumor throughout the body could potentially provide more comprehensive information to predict whether a patient will respond to cetuximab treatment
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
