Development and evaluation of a cetuximab-based imaging probe to target EGFR and EGFRvIII.

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.