EGFR-targeted multi-modal molecular imaging and treatment in a heterocellular model of head and neck cancer

Abstract

Precision molecular imaging finds application in the delineation of tumor margins during surgical resection of head and neck cancers (HNCs). Despite the advantages of surgery, there remain challenges in successfully locating tumor margins, resecting the entire tumor volume and treatment of microscopic tumor tissue. The presence of residual tumors, post-surgery, may require additional interventions and often lead to tumor recurrence. While Epidermal growth factor receptor (EGFR) remains a receptor of choice for targeting in HNCs, the heterogeneity in the expression of EGFR often leads to variations in response to targeted therapeutics. To improve visualization and tumor margin delineation during head and neck tumor surgeries, this study demonstrates the development of a molecular targeted theranostic probe combining the complementary features of fluorescence and photoacoustic imaging. The probe: DFAC (Dual Function Antibody Conjugate) comprises of a fluorophore/photosensitizer; Benzoporphyrin derivative (BPD) and a photoacoustic contrast agent; naphthalocyanine (NC) derivative conjugated to an EGFR antibody; Cetuximab. While BPD assists in fluorescence imaging, it can also be used for inducing cytotoxicity, through photodynamic activation in target tissues. The efficacy of DFAC in selective visualization and photodynamic therapy of tumor cells is evaluated on heterocellular 3D tumor spheroids and orthotopic mouse tongue tumors developed from human oral cancer cell lines (CAL27 and SCC4), expressing different levels of EGFR. In summary, this study demonstrates the potential of the theranostic probe (DFAC) to delineate tumor regions for guiding surgical resection and eradicate residual tumor tissue (post-surgery) by photodynamic therapy.