Leonie Bruine de Bruin1, Vikram R Bollineni2, Jan E Wachters1, Ed Schuuring3, Bettien M van Hemel3, Jacqueline E van der Wal4, Lorian Slagter-Menkema3, Geertruida H de Bock5, Roel J H M Steenbakkers6, Johannes A Langendijk6, Jan Pruim7, Bernard F A M van der Laan8, Gyorgy B Halmos9. 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.
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.
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.
Authors: Seth T Gammon; Federica Pisaneschi; Madhavi L Bandi; Melinda G Smith; Yuting Sun; Yi Rao; Florian Muller; Franklin Wong; John De Groot; Jeffrey Ackroyd; Osama Mawlawi; Michael A Davies; Y N Vashisht Gopal; M Emilia Di Francesco; Joseph R Marszalek; Mark Dewhirst; David Piwnica-Worms Journal: Cells Date: 2019-11-21 Impact factor: 6.600