Imaging of tumour hypoxia and metabolism in patients with head and neck squamous cell carcinoma

ABSTRACT

Background. Tumour hypoxia and a high tumour metabolism increase radioresistance in patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to evaluate the correlation between hypoxia ([¹⁸F]HX4 PET) and glucose metabolism ([¹⁸F]FDG PET) molecular imaging.

Material and methods. [¹⁸F]HX4 and [¹⁸F]FDG PET/CT images of 20 HNSCC patients were acquired prior to (chemo)radiotherapy, in an immobilisation mask, with a median time interval of seven days (NCT01347281). Gross tumour volumes of the primary lesions (GTV_prim) and pathological lymph nodes (GTV_ln) were included in the analysis. [¹⁸F]FDG PET/CT images were rigidly registered to the [¹⁸F]HX4 PET/CT images. The maximum and mean standardised uptake values (SUV_max, SUV_mean) within both GTVs were determined. In addition, the overlap was compared between the [¹⁸F]HX4 high volume ([¹⁸F]HX4 HV) with a tumour-to-muscle ratio > 1.4 and the [¹⁸F]FDG high volume ([¹⁸F]FDG HV) with an SUV > 50% of the SUV_max. We report the mean± standard deviation.

Results. PET/CT scans including 20 GTV_prim and 12 GTV_lnwere analysed. There was a significant correlation between several [¹⁸F]FDG and [¹⁸F]HX4 parameters, the most pronounced being the correlation between [¹⁸F]FDG HV and [¹⁸F]HX4 HV (R = 0.93, p < 0.001). The fraction of the GTV_prim with a high HX4 uptake (9 ± 10%) was on average smaller than the FDG high fraction (51 ± 26%; p < 0.001). In 65% (13/20) of the patients, the GTV_prim was hypoxic. In four of these patients the [¹⁸F]HX4 HV was located within the [¹⁸F]FDG HV, whereas for the remaining nine GTV_prim a partial mismatch was observed. In these nine tumours 25 ± 21% (range 5–64%) of the HX4 HV was located outside the FDG HV.

Conclusions. There is a correlation between [¹⁸F]HX4 and [¹⁸F]FDG uptake parameters on a global tumour level. In the majority of lesions a partial mismatch between the [¹⁸F]HX4 and [¹⁸F]FDG high uptake volumes was observed, therefore [¹⁸F]FDG PET imaging cannot be used as a surrogate for hypoxia. [¹⁸F]HX4 PET provides complementary information to [¹⁸F]FDG PET imaging.

Acknowledgements

The authors like to thank the patients who agreed to participate to this study and the PET-CT group, data-management (Anita Botterweck) and trial-poli (Claudia Offermann and John Paulissen) of MAASTRO clinic for their contribution to the data acquisition. Authors acknowledge financial support from the QuIC-ConCePT project, which is partly funded by EFPI A companies and the Innovative Medicine Initiative Joint Undertaking (IMI JU) under Grant Agreement No. 115151. Authors also acknowledge financial support from EU 7th framework program (EURECA, ARTFORCE – no. 257144, REQUITE – no. 601826), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF MAC 2011-4970).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Figure 1 and 2 available online at http://www.informahealthcare.com/doi/abs/10.3109/0284186X.2015.1062913