TY - JOUR
T1 - Translation of c‐met targeted image‐guided surgery solutions in oral cavity cancer—initial proof of concept data
AU - Buckle, Tessa
AU - van Alphen, Maarten
AU - van Oosterom, Matthias N.
AU - van Beurden, Florian
AU - Heimburger, Nina
AU - van der Wal, Jaqueline E.
AU - van den Brekel, Michiel
AU - van Leeuwen, Fijs W.B.
AU - Karakullukcu, Baris
N1 - Funding Information: Funding: This research was financially supported by a Netherlands Organization for Scientific Re‐ search TTW‐VICI grant (Grant No. TTW 16141). EMI‐137 was provided by Edinburgh Molecular Imaging (EMI), and Karl Storz Endoskope GmbH provided the Cy5 fluorescence camera. Funding Information: This research was financially supported by a Netherlands Organization for Scientific Research TTW?VICI grant (Grant No. TTW 16141). EMI?137 was provided by Edinburgh Molecular Imaging (EMI), and Karl Storz Endoskope GmbH provided the Cy5 fluorescence camera. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - C‐Met
KW - Fluorescence
KW - Head and neck cancer
KW - Image‐guided surgery
KW - Molecular imaging
UR - http://www.scopus.com/inward/record.url?scp=85106658920&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers13112674
DO - https://doi.org/10.3390/cancers13112674
M3 - Article
C2 - 34071623
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 11
M1 - 2674
ER -
