Immuno-PET imaging based radioimmunotherapy in head and neck squamous cell carcinoma model

Abstract

The epidermal growth factor receptor (EGFR) is one of the most comprehensively studied molecular targets in head and neck squamous cell carcinoma (HNSCC). However, inherent and acquired resistance are serious problems and are responsible for limited clinical efficacy and tumor recurrence. In this study, we evaluated the feasibility of immuno-positron emission tomography (PET) imaging and radioimmunotherapy (RIT) with ⁶⁴Cu-/¹⁷⁷Lu-PCTA-cetuximab in cetuximab-resistant SNU-1066 HNSCC xenografted model. The cellular uptake of ⁶⁴Cu/¹⁷⁷Lu-3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid (PCTA)-cetuximab showed good correlation with western blot and flow cytometry analysis in EGFR expression level of various HNSCC cells. ¹⁷⁷Lu-PCTA-cetuximab selectively killed cetuximab-resistant SNU-1066 cells in vitro. ⁶⁴Cu-/¹⁷⁷Lu-PCTA-cetuximab specifically accumulated in SNU-1066 tumor and those uptakes were peaked at 48 h and 7 day, respectively in biodistribution, PET and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. RIT with single dose of ¹⁷⁷Lu-PCTA-cetuximab exhibited significant tumor regression and markedly reduced 2-[¹⁸F]fluoro-2-deoxy-D-glucose (¹⁸F-FDG) uptake, compared to other groups. Proliferation index were dramatically decreased and apoptotic index increased in RIT group. These results suggest that a diagnostic and therapeutic convergence radiopharmaceutical, ⁶⁴Cu-/¹⁷⁷Lu-PCTA-cetuximab has the potential of target selection using immuno-PET imaging and targeted therapy by RIT in EGFR expressing cetuximab-resistant HNSCC tumors.