Maxime D Slooter1, Henricus J M Handgraaf2, Martin C Boonstra2, Lily-Ann van der Velden3, Shadhvi S Bhairosingh2, Ivo Que4, Lorraine M de Haan5, Stijn Keereweer6, Pieter B A A van Driel7, Alan Chan8, Hisataka Kobayashi9, Alexander L Vahrmeijer2, Clemens W G M Löwik7. 1. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.slooter@lumc.nl. 2. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. 3. Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of Head and Neck Oncology and Surgery, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Amsterdam, The Netherlands. 4. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. 5. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. 6. Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. 7. Optical Molecular Imaging, Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands. 8. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Percuros B.V., Enschede, The Netherlands. 9. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, USA.
Abstract
OBJECTIVES: Tumour-positive resection margins are a major problem during oral cancer surgery. gGlu-HMRG is a tracer that becomes fluorescent upon activation by gamma-glutamyltranspeptidase (GGT). This study aims to investigate the combination of gGlu-HMRG and a clinical fluorescence imaging system for the detection of tumour-positive resection margins. MATERIALS AND METHODS: The preclinical Maestro and clinical Artemis imaging systems were compared in vitro and ex vivo with cultured human head and neck cancer cells (OSC19, GGT-positive; and FaDu, GGT negative) and tumour-bearing nude mice. Subsequently, frozen sections of normal and oral cancer tissues were ex vivo sprayed with gGlu-HMRG to determine the sensitivity and specificity. Finally, resection margins of patients with suspected oral cancer were ex vivo sprayed with gGlu-HMRG to detect tumour-positive resection margins. RESULTS: Both systems could be used to detect gGlu-HMRG activation in vitro and ex vivo in GGT positive cancer cells. Sensitivity and specificity of gGlu-HMRG and the Artemis on frozen tissue samples was 80% and 87%, respectively. Seven patients undergoing surgery for suspected oral cancer were included. In three patients fluorescence was observed at the resection margin. Those margins were either tumour-positive or within 1 mm of tumour. The margins of the other patients were clear (≥8 mm). CONCLUSION: This study demonstrates the feasibility to detect tumour-positive resection margins with gGlu-HMRG and a clinical fluorescence imaging system. Applying this technique would enable intraoperative screening of the entire resection margin and allow direct re-resection in case of tumour-positivity.
OBJECTIVES:Tumour-positive resection margins are a major problem during oral cancer surgery. gGlu-HMRG is a tracer that becomes fluorescent upon activation by gamma-glutamyltranspeptidase (GGT). This study aims to investigate the combination of gGlu-HMRG and a clinical fluorescence imaging system for the detection of tumour-positive resection margins. MATERIALS AND METHODS: The preclinical Maestro and clinical Artemis imaging systems were compared in vitro and ex vivo with cultured humanhead and neck cancer cells (OSC19, GGT-positive; and FaDu, GGT negative) and tumour-bearing nude mice. Subsequently, frozen sections of normal and oral cancer tissues were ex vivo sprayed with gGlu-HMRG to determine the sensitivity and specificity. Finally, resection margins of patients with suspected oral cancer were ex vivo sprayed with gGlu-HMRG to detect tumour-positive resection margins. RESULTS: Both systems could be used to detect gGlu-HMRG activation in vitro and ex vivo in GGT positive cancer cells. Sensitivity and specificity of gGlu-HMRG and the Artemis on frozen tissue samples was 80% and 87%, respectively. Seven patients undergoing surgery for suspected oral cancer were included. In three patients fluorescence was observed at the resection margin. Those margins were either tumour-positive or within 1 mm of tumour. The margins of the other patients were clear (≥8 mm). CONCLUSION: This study demonstrates the feasibility to detect tumour-positive resection margins with gGlu-HMRG and a clinical fluorescence imaging system. Applying this technique would enable intraoperative screening of the entire resection margin and allow direct re-resection in case of tumour-positivity.
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