title: Assessment of hypoxic subvolumes in laryngeal cancer with (18)F-fluoroazomycinarabinoside ((18)F-FAZA)-PET/CT scanning and immunohistochemistry.
abstract: OBJECTIVE
  (18)F-fluoroazomycinarabinoside ((18)F-FAZA) is a promising hypoxia radiopharmaceutical agent with outstanding biokinetic parameters. We aimed to determine the accuracy of (18)F-FAZA-PET/CT scan in detecting hypoxic regions within the tumor using immunohistochemical markers in a pilot study.
  
  
  METHODS
  Eleven patients with primary or recurrent laryngeal squamous cell carcinoma were indicated for total laryngectomy (TLE). Patients underwent (18)F-FAZA-PET/CT scan before TLE. Hypoxic regions inside the laryngeal tumor were determined. After TLE, regions with high uptake on (18)F-FAZA-PET scan were selected for immunohistochemical examination for exogenous (pimonidazole) and endogenous (HIF1α, CA-IX and GLUT-1) hypoxia markers. To assess the accuracy of (18)F-FAZA-PET scanning, radiopharmacon accumulation was related with immunohistochemical expression of hypoxia markers.
  
  
  RESULTS
  Inter- and intratumoral heterogeneity of tumor hypoxia was observed on (18)F-FAZA-PET scan. Nine of the eleven tumors were hypoxic with (18)F-FAZA-PET. Hypoxia could also be detected with pimonidazole, HIF1α, CA-IX and GLUT-1 expression in some tumors. No clear association was observed between (18)F-FAZA uptake and hypoxia markers.
  
  
  CONCLUSIONS
  This pilot study could not prove the accuracy of (18)F-FAZA-PET in determining hypoxic subvolumes in laryngeal cancer. Further study is required to investigate the benefit of (18)F-FAZA-PET imaging in radiotherapy planning.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Groningen, University Medical Center Groningen, The Netherlands; Graduate School of Medical Sciences (Damage and Repair in Cancer Development and Cancer Treatment), University of Groningen, The Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: Bruine de Bruin
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, The Netherlands and Department of Nuclear Medicine, Tygerberg Hospital, Stellenbosch University, South Africa.
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Bollineni
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Groningen, University Medical Center Groningen, The Netherlands; Graduate School of Medical Sciences (Damage and Repair in Cancer Development and Cancer Treatment), University of Groningen, The Netherlands.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Wachters
authors.affiliation: Department of Pathology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
authors.affiliation: Department of Pathology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Bettien M
authors.initials: BM
authors.lastname: van Hemel
authors.affiliation: Department of Pathology, University of Groningen, University Medical Center Groningen, The Netherlands; Department of Pathology, Martini Hospital Groningen, The Netherlands.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: van der Wal
authors.affiliation: Department of Pathology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Lorian
authors.initials: L
authors.lastname: Slagter-Menkema
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Roel J H M
authors.initials: RJ
authors.lastname: Steenbakkers
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, The Netherlands and Department of Nuclear Medicine, Tygerberg Hospital, Stellenbosch University, South Africa.
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Bernard F A M
authors.initials: BF
authors.lastname: van der Laan
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: g.b.halmos@umcg.nl.
authors.forename: Gyorgy B
authors.initials: GB
authors.lastname: Halmos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000175:diagnosis / Q000601:surgery; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000601:surgery; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis / Q000209:etiology*; D007822:Laryngeal Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000601:surgery; D007825:Laryngectomy; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy; D009593:Nitroimidazoles; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D000077195:Squamous Cell Carcinoma of Head and Neck; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D015415:Biomarkers; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C498052:fluoroazomycin arabinoside; C033815:pimonidazole
keywords: (18)F-FAZA-PET; Hypoxia markers; Laryngeal cancer; Tumor hypoxia