title: 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 ([(18)F]HX4 PET) and glucose metabolism ([(18)F]FDG PET) molecular imaging.
  
  
  METHODS
  [(18)F]HX4 and [(18)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 (GTVprim) and pathological lymph nodes (GTVln) were included in the analysis. [(18)F]FDG PET/CT images were rigidly registered to the [(18)F]HX4 PET/CT images. The maximum and mean standardised uptake values (SUVmax, SUVmean) within both GTVs were determined. In addition, the overlap was compared between the [(18)F]HX4 high volume ([(18)F]HX4 HV) with a tumour-to-muscle ratio > 1.4 and the [(18)F]FDG high volume ([(18)F]FDG HV) with an SUV > 50% of the SUVmax. We report the mean ± standard deviation.
  
  
  RESULTS
  PET/CT scans including 20 GTVprim and 12 GTVln were analysed. There was a significant correlation between several [(18)F]FDG and [(18)F]HX4 parameters, the most pronounced being the correlation between [(18)F]FDG HV and [(18)F]HX4 HV (R = 0.93, p < 0.001). The fraction of the GTVprim 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 GTVprim was hypoxic. In four of these patients the [(18)F]HX4 HV was located within the [(18)F]FDG HV, whereas for the remaining nine GTVprim 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 [(18)F]HX4 and [(18)F]FDG uptake parameters on a global tumour level. In the majority of lesions a partial mismatch between the [(18)F]HX4 and [(18)F]FDG high uptake volumes was observed, therefore [(18)F]FDG PET imaging cannot be used as a surrogate for hypoxia. [(18)F]HX4 PET provides complementary information to [(18)F]FDG PET imaging.
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Catharina M L
authors.initials: CM
authors.lastname: Zegers
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: van Elmpt
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Frank J P
authors.initials: FJ
authors.lastname: Hoebers
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.|b Helmholtz Zentrum Dresden-Rossendorf , Dresden , Germany.|c OncoRay, Department of Radiation Oncology , Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden , Dresden , Germany.
authors.forename: Esther G C
authors.initials: EG
authors.lastname: Troost
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Öllers
authors.affiliation: d Department of Nuclear Medicine , Maastricht University Medical Centre , Maastricht , The Netherlands.|e Department of Nuclear Medicine , RWTH Aachen University, University Hospital , Aachen , Germany.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging*; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging*; D007090:Image Interpretation, Computer-Assisted; D007093:Imidazoles / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014230:Triazoles / Q000493:pharmacokinetics*
chemical_list: C562168:HX4 compound; D007093:Imidazoles; D019275:Radiopharmaceuticals; D014230:Triazoles; D019788:Fluorodeoxyglucose F18