Cytotoxic properties of radionuclide-conjugated Cetuximab without and in combination with external irradiation in head and neck cancer cells in vitro.

Purpose: Epidermal growth factor receptor (EGFR) is critically involved in progression and therapy resistance of squamous cell carcinoma (SCC). Albeit EGFR targeting could improve the effect of radiotherapy on patients' outcome, the clinical results failed to meet expectations from preclinical studies. In this work, we evaluated the potential of the radionuclide Yttrium-90 (⁹⁰Y) bound to Cetuximab (⁹⁰Y-Cetuximab) as novel targeting approach for SCC cells in vitro. Materials and methods: FaDu and A431 cell lines were used. EGFR subcellular localization, clonogenic survival, radiation-induced γH2AX foci and EGFR signaling were examined. Cells were treated with DTPA, DTPA-Cetuximab, ⁹⁰Y and ⁹⁰Y-Cetuximab alone or in combination with external X-ray irradiation. Results: Dose- and cell line-dependently, ⁹⁰Y-Cetuximab mediated a significant reduction in clonogenicity relative to unbound ⁹⁰Y. Combined 2-Gy external radiation plus 2-Gy equivalent dose of ⁹⁰Y-Cetuximab was more effective than equivalent doses of ⁹⁰Y and X-ray radiation. Analogous effects were observed in the number of residual radiation-induced foci. Additionally, EGFR, ERK1/2 and AKT phosphorylation showed alterations upon different treatments. Conclusions: Our findings show that Cetuximab-conjugated ⁹⁰Y has a significant potential to eradicate human SCC cells. A combination of radioimmunotherapeutic compounds and external radiotherapy might be a promising treatment strategy for clinical application. [ABSTRACT FROM AUTHOR]