Translation of c‐met targeted image‐guided surgery solutions in oral cavity cancer—initial proof of concept data

Abstract

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 suita-bility 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 pro-cessing software allowed video‐rate assessment of the tumor‐to‐background ratio (TBR). Fluorescence imaging results were related to standard pathological evaluation and c‐MET immunohisto-chemistry. After incubation with EMI‐137, 9/10 tumors were fluorescently illuminated. Immuno-histochemistry 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.