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

<div><p>ABSTRACT</p><p><b>Background.</b> 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 ([<sup>18</sup>F]HX4 PET) and glucose metabolism ([<sup>18</sup>F]FDG PET) molecular imaging.</p><p><b>Material and methods.</b> [<sup>18</sup>F]HX4 and [<sup>18</sup>F]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<sub>prim</sub>) and pathological lymph nodes (GTV<sub>ln</sub>) were included in the analysis. [<sup>18</sup>F]FDG PET/CT images were rigidly registered to the [<sup>18</sup>F]HX4 PET/CT images. The maximum and mean standardised uptake values (SUV<sub>max</sub>, SUV<sub>mean</sub>) within both GTVs were determined. In addition, the overlap was compared between the [<sup>18</sup>F]HX4 high volume ([<sup>18</sup>F]HX4 HV) with a tumour-to-muscle ratio > 1.4 and the [<sup>18</sup>F]FDG high volume ([<sup>18</sup>F]FDG HV) with an SUV > 50% of the SUV<sub>max</sub>. We report the mean± standard deviation.</p><p><b>Results.</b> PET/CT scans including 20 GTV<sub>prim</sub> and 12 GTV<sub>ln</sub>were analysed. There was a significant correlation between several [<sup>18</sup>F]FDG and [<sup>18</sup>F]HX4 parameters, the most pronounced being the correlation between [<sup>18</sup>F]FDG HV and [<sup>18</sup>F]HX4 HV (R = 0.93, p < 0.001). The fraction of the GTV<sub>prim</sub> 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<sub>prim</sub> was hypoxic. In four of these patients the [<sup>18</sup>F]HX4 HV was located within the [<sup>18</sup>F]FDG HV, whereas for the remaining nine GTV<sub>prim</sub> a partial mismatch was observed. In these nine tumours 25 ± 21% (range 5–64%) of the HX4 HV was located outside the FDG HV.</p><p><b>Conclusions.</b> There is a correlation between [<sup>18</sup>F]HX4 and [<sup>18</sup>F]FDG uptake parameters on a global tumour level. In the majority of lesions a partial mismatch between the [<sup>18</sup>F]HX4 and [<sup>18</sup>F]FDG high uptake volumes was observed, therefore [<sup>18</sup>F]FDG PET imaging cannot be used as a surrogate for hypoxia. [<sup>18</sup>F]HX4 PET provides complementary information to [<sup>18</sup>F]FDG PET imaging.</p></div>