Assessment of hypoxic subvolumes in laryngeal cancer with (18)F-fluoroazomycinarabinoside ((18)F-FAZA)-PET/CT scanning and immunohistochemistry

Leonie Bruine de Bruin; Vikram R Bollineni; Jan E Wachters; Ed Schuuring; Bettien M van Hemel; Jacqueline E van der Wal; Lorian Slagter-Menkema; Geertruida H de Bock; Roel J H M Steenbakkers; Johannes A Langendijk; Jan Pruim; Bernard F A M van der Laan; Gyorgy B Halmos

doi:10.1016/j.radonc.2015.07.012

Assessment of hypoxic subvolumes in laryngeal cancer with (18)F-fluoroazomycinarabinoside ((18)F-FAZA)-PET/CT scanning and immunohistochemistry

Radiother Oncol. 2015 Oct;117(1):106-12. doi: 10.1016/j.radonc.2015.07.012. Epub 2015 Aug 3.

Affiliations

¹ 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.
² 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.
³ Department of Pathology, University of Groningen, University Medical Center Groningen, The Netherlands.
⁴ Department of Pathology, University of Groningen, University Medical Center Groningen, The Netherlands; Department of Pathology, Martini Hospital Groningen, The Netherlands.
⁵ Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands.
⁶ Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
⁷ 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.
⁸ Department of Otolaryngology, Head and Neck Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
⁹ Department of Otolaryngology, Head and Neck Surgery, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: g.b.halmos@umcg.nl.

PMID: 26250803
DOI: 10.1016/j.radonc.2015.07.012

Abstract

Background and purpose: (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.

Patients and 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.

Keywords: (18)F-FAZA-PET; Hypoxia markers; Laryngeal cancer; Tumor hypoxia.

Publication types

Evaluation Study

MeSH terms

Aged
Aged, 80 and over
Biomarkers / metabolism
Carcinoma, Squamous Cell / complications*
Carcinoma, Squamous Cell / diagnosis
Carcinoma, Squamous Cell / surgery
Female
Head and Neck Neoplasms / complications*
Head and Neck Neoplasms / diagnosis
Head and Neck Neoplasms / surgery
Humans
Hypoxia / diagnosis
Hypoxia / etiology*
Laryngeal Neoplasms / complications*
Laryngeal Neoplasms / diagnosis
Laryngeal Neoplasms / surgery
Laryngectomy
Male
Middle Aged
Multimodal Imaging / methods
Neoplasm Recurrence, Local / radiotherapy
Nitroimidazoles
Pilot Projects
Positron-Emission Tomography / methods
Prospective Studies
Radiopharmaceuticals
Squamous Cell Carcinoma of Head and Neck
Tomography, X-Ray Computed / methods

Substances

Biomarkers
Nitroimidazoles
Radiopharmaceuticals
fluoroazomycin arabinoside
pimonidazole