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Article

Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data

1
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
2
Department of Head and Neck Surgery and Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
3
Department of Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: Juan P. Rodrigo
Cancers 2021, 13(11), 2674; https://doi.org/10.3390/cancers13112674
Received: 22 April 2021 / Revised: 19 May 2021 / Accepted: 27 May 2021 / Published: 28 May 2021
(This article belongs to the Special Issue Surgical Treatment of Head and Neck Squamous Cell Carcinomas (HNSCC))
Translation of tumor-specific fluorescent tracers is crucial in the realization intraoperative of tumor identification during fluorescence-guided surgery. Ex vivo assessment of surgical specimens after topical tracer application has the potential to reveal the suitability of a potential surgical target prior to in vivo use in patients. In this study, the c-Met receptor was identified as a possible candidate for fluorescence-guided surgery in oral cavity cancer. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In total, 9/10 tumors were fluorescently illuminated, while non-visualization could be linked to non-superficial tumor localization. Immunohistochemistry revealed c-Met expression in all ten specimens. Tumor assessment was improved via video representation of the tumor-to-background ratio.
Intraoperative tumor identification (extension/margins/metastases) via receptor-specific targeting is one of the ultimate promises of fluorescence-guided surgery. The translation of fluorescent tracers that enable tumor visualization forms a critical component in the realization of this approach. Ex vivo assessment of surgical specimens after topical tracer application could help provide an intermediate step between preclinical evaluation and first-in-human trials. Here, the suitability of the c-Met receptor as a potential surgical target in oral cavity cancer was explored via topical ex vivo application of the fluorescent tracer EMI-137. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In-house developed image processing software allowed video-rate assessment of the tumor-to-background ratio (TBR). Fluorescence imaging results were related to standard pathological evaluation and c-MET immunohistochemistry. After incubation with EMI-137, 9/10 tumors were fluorescently illuminated. Immunohistochemistry revealed c-Met expression in all ten specimens. Non-visualization could be linked to a more deeply situated lesion. Tumor assessment was improved via video representation of the TBR (median TBR: 2.5 (range 1.8–3.1)). Ex vivo evaluation of tumor specimens suggests that c-Met is a possible candidate for fluorescence-guided surgery in oral cavity cancer. View Full-Text
Keywords: molecular imaging; fluorescence; image-guided surgery; c-Met; head and neck cancer molecular imaging; fluorescence; image-guided surgery; c-Met; head and neck cancer
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MDPI and ACS Style

Buckle, T.; van Alphen, M.; van Oosterom, M.N.; van Beurden, F.; Heimburger, N.; van der Wal, J.E.; van den Brekel, M.; van Leeuwen, F.W.B.; Karakullukcu, B. Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data. Cancers 2021, 13, 2674. https://doi.org/10.3390/cancers13112674

AMA Style

Buckle T, van Alphen M, van Oosterom MN, van Beurden F, Heimburger N, van der Wal JE, van den Brekel M, van Leeuwen FWB, Karakullukcu B. Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data. Cancers. 2021; 13(11):2674. https://doi.org/10.3390/cancers13112674

Chicago/Turabian Style

Buckle, Tessa, Maarten van Alphen, Matthias N. van Oosterom, Florian van Beurden, Nina Heimburger, Jaqueline E. van der Wal, Michiel van den Brekel, Fijs W.B. van Leeuwen, and Baris Karakullukcu. 2021. "Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data" Cancers 13, no. 11: 2674. https://doi.org/10.3390/cancers13112674

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