In vitro measurement of glucose uptake after radiation and cetuximab treatment in head and neck cancer cell lines using 18F-FDG, gamma spectrometry and PET/CT

Abstract

The standard treatment for head and neck squamous cell carcinoma (HNSCC) is radiotherapy, often in combination with chemotherapy or surgery. However, a novel monoclonal antibody, cetuximab (Erbitux®), has also been approved for patient therapy. The aim of present study was to develop an in vitro method for the measurement of 18F-fluoro-2deoxy-D-glucose (FDG) to determine if cellular 18F-FDG uptake is associated with response to radiotherapy or cetuximab treatment. In the current study, HNSCC cell lines were treated with radiation or with cetuximab. Next, the uptake of 18F-FDG was measured using a gamma spectrometer (GS). Thereafter, uptake after radiation was measured first with GS and then compared with positron emission tomography (PET)/computed tomography (CT) imaging. Furthermore, the mRNA expression of glucose transporter 1 (GLUT1) was measured following cetuximab treatment via reverse transcription-quantitative PCR. A study protocol was developed to measure the cellular uptake of 18F-FDG via gamma-ray spectrometry and comparable results were obtained with those of clinical PET/CT. The results revealed a decrease in 18F-FDG after radiation and cetuximab treatment. The uptake of 18F-FDG following cetuximab treatment was significantly lower in the cetuximab-sensitive cell line UT-SCC-14 compared with the cetuximab-resistant cell lines UT-SCC-2 and UT-SCC-45. Furthermore, after treatment with cetuximab for 24 and 48 h, a significant increase in GLUT1 expression was detected in the sensitive cell line compared with the two resistant cell lines. In conclusion, a novel yet reliable method for the measurement of intracellular 18F-FDG via GS has been developed, and our results indicate that 18F-FDG uptake is associated with radiation and cetuximab response in HNSCC.