Repeatability of hypoxia PET imaging using [18F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Catharina M.L. Zegers, Wouter van Elmpt, Katrin Szardenings, Hartmuth Kolb, Alan Waxman, Rathan M. Subramaniam, Dae Hyuk Moon, Jacqueline C. Brunetti, Shyam M. Srinivas, Philippe Lambin, David Chien

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Purpose: Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [18F]HX4 in patients with head and neck and lung cancer. Methods: Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [18F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUVmax and SUVmean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient. Results: All parameters of [18F]HX4 uptake were significantly correlated between scans: SUVmax (r = 0.958, p < 0.001), SUVmean (r = 0.946, p < 0.001), TBRmax (r = 0.962, p < 0.001) and HV1.2 (r = 0.995, p < 0.001). The relative coefficients of repeatability were 15 % (SUVmean), 17 % (SUVmax) and 17 % (TBRmax). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65 ± 0.14. Conclusion: Repeated hypoxia PET scans with [18F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [18F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

Original languageEnglish (US)
Pages (from-to)1840-1849
Number of pages10
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number12
StatePublished - Nov 1 2015


  • HX4
  • Head and neck cancer
  • Hypoxia
  • Lung cancer
  • PET imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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