title: Repeatability of hypoxia PET imaging using [¹⁸F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial.
abstract: OBJECTIVE
  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 [(18)F]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 [(18)F]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 [(18)F]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.
  
  
  CONCLUSIONS
  Repeated hypoxia PET scans with [(18)F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [(18)F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands. Karen.zegers@maastro.nl.
authors.forename: Catharina M L
authors.initials: CM
authors.lastname: Zegers
authors.affiliation: 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: Threshold Pharmaceuticals, 170 Harbor Way, South San Francisco, CA, 94080, USA.
authors.forename: Katrin
authors.initials: K
authors.lastname: Szardenings
authors.affiliation: Siemens Molecular Imaging Biomarker Research, Siemens Medical Solutions USA, Inc., 6100 Bristol Parkway, Culver City, CA, USA.
authors.forename: Hartmuth
authors.initials: H
authors.lastname: Kolb
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Waxman
authors.affiliation: Boston University School of Medicine, Boston, MA, USA.|Division of Nuclear Medicine, Russell H Morgan Department of Radiology and Radiologic Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Rathan M
authors.initials: RM
authors.lastname: Subramaniam
authors.affiliation: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Dae Hyuk
authors.initials: DH
authors.lastname: Moon
authors.affiliation: Holy Name Medical Center, Teaneck, NJ, USA.
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Brunetti
authors.affiliation: Department of Nuclear Medicine, Imaging Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
authors.forename: Shyam M
authors.initials: SM
authors.lastname: Srinivas
authors.affiliation: 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
authors.affiliation: Siemens Molecular Imaging Biomarker Research, Siemens Medical Solutions USA, Inc., 6100 Bristol Parkway, Culver City, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chien
mesh_terms: D000368:Aged; D001692:Biological Transport; D015687:Cell Hypoxia; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000378:metabolism; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D015203:Reproducibility of Results; D014230:Triazoles / Q000378:metabolism
chemical_list: C553729:3-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol; D009593:Nitroimidazoles; D014230:Triazoles
keywords: HX4; Head and neck cancer; Hypoxia; Lung cancer; PET imaging