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Published on: August 14, 2018
Development and evaluation of a cetuximab-based imaging probe to target EGFR and EGFRvIII
Hugo J W L Aerts1, Ludwig Dubois, Tilman M Hackeng
1Department of Radiation Oncology (MAASTRO), GROW Research Institute, University of Maastricht, The Netherlands. Hugo.Aerts@maastro.nl
Background And Purpose:
The epidermal growth factor receptor (EGFR) is overexpressed in a significant percentage of human malignancies and its expression is associated with tumour aggressiveness and treatment resistance. The monoclonal antibody cetuximab (IMC-C225) blocks the ligand-binding domain of EGFR with high affinity, preventing downstream signalling resulting in tumour growth inhibition. We developed and characterized a novel imaging probe using Oregon Green 488 labelled cetuximab to evaluate its usage as an imaging agent to target EGFR.
Materials And Methods:
Cells with varying expression levels of EGFR or a mutant form of EGFR, called EGFRvIII, were used for in vitro validation. The in vivo binding of labelled cetuximab to EGFR was also assessed ex vivo on tumour material.
Results:
The development of Oregon Green 488 labelled cetuximab was successful, demonstrating binding to both EGFR and EGFRvIII in vitro. Accumulation was also found in vivo, which was confirmed by histopathology using anti-EGFR antibodies. However, significant mismatch highlights differences between drug delivery in vivo, and cell expression levels of EGFR.
Conclusions:
The monoclonal antibody cetuximab represents a promising probe to evaluate the biologic and pharmacokinetic effects of in vivo cetuximab binding to EGFR. It not only visualizes the presence of the wild type EGFR, but also the presence of the mutant EGFRvIII.
Insights
Researchers developed a novel imaging probe using Oregon Green 488 labeled cetuximab to target the epidermal growth factor receptor (EGFR). This probe successfully visualized both wild-type and mutant EGFR in vitro and in vivo.
Area of Science:
- Oncology
- Molecular Imaging
- Biochemistry
Background:
- Epidermal growth factor receptor (EGFR) overexpression is linked to cancer aggressiveness and treatment resistance.
- Cetuximab (IMC-C225) is a monoclonal antibody that inhibits EGFR signaling, impeding tumor growth.
Purpose of the Study:
- To develop and characterize a novel imaging probe using Oregon Green 488 labeled cetuximab.
- To evaluate the probe's utility for targeting and visualizing EGFR in malignancies.
Main Methods:
- In vitro validation using cells with varying EGFR expression levels, including mutant EGFRvIII.
- In vivo assessment of labeled cetuximab binding to EGFR ex vivo on tumor tissue.
Main Results:
- Successful development of Oregon Green 488 labeled cetuximab.
- Demonstrated in vitro binding to both wild-type EGFR and EGFRvIII.
- Observed in vivo accumulation confirmed by histopathology, though with noted discrepancies between drug delivery and EGFR expression levels.
Conclusions:
- Labeled cetuximab is a promising probe for evaluating in vivo EGFR binding.
- The probe visualizes both wild-type and mutant EGFR (EGFRvIII).
- Highlights the need to consider differences in in vivo drug delivery versus cellular expression levels.
