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.

Fluorescence, Head and neck neoplasms, Margins of excision, Optical imaging, Oral cavity, Squamous cell carcinoma
dx.doi.org/10.1016/j.oraloncology.2017.12.006, hdl.handle.net/1765/105590
Oral Oncology
This work was funded by the European Commission 7th Framework Programme; grant id h2020/644373 - Preclinical Intra-Operative Image-Guided Surgery and Post-Operative Radiotherapy of Tumours (PRISAR)
Department of Otorhinolaryngology

Slooter, M.D, Handgraaf, H.J.M. (Henricus J.M.), Boonstra, M.C, van der Velden, L.-A. (Lily-Ann), Bhairosingh, S.S. (Shadhvi S.), Que, I, … Löwik, C.W.G.M. (2018). Detecting tumour-positive resection margins after oral cancer surgery by spraying a fluorescent tracer activated by gamma-glutamyltranspeptidase. Oral Oncology, 78, 1–7. doi:10.1016/j.oraloncology.2017.12.006