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Toward operative in vivo fluorescence imaging of the c‐ M et proto‐oncogene for personalization of therapy in ovarian cancer
Author(s) -
Liu Shujuan,
Zheng Yong,
Volpi Davide,
ElKasti Muna,
Klotz Daniel,
Tullis Iain,
Henricks Andrea,
Campo Leticia,
Myers Kevin,
Laios Alex,
Thomas Peter,
Ng Tony,
Dhar Sunanda,
Becker Christian,
Vojnovic Borivoj,
Ahmed Ahmed Ashour
Publication year - 2015
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.29029
Subject(s) - ovarian cancer , medicine , in vivo , cancer research , cancer , oncogene , pathology , biology , cell cycle , microbiology and biotechnology
BACKGROUND Standard biomarker testing of a single macroscopic disease site is unlikely to be sufficient because of tumor heterogeneity. A focus on examining global biomarker expression or activity, particularly in microscopic residual chemotherapy‐resistant disease, is needed for the appropriate selection of targeted therapies. This study was aimed at establishing a technique for the assessment of biomarkers of ovarian cancer peritoneal spread. METHODS An in‐house developed fluorescent imaging device was used to detect the expression of the c‐Met oncogene in ovarian cancer. A modified cyanine 5–tagged peptide, GE137, with a high in vitro affinity for the human c‐Met protein, was tested in a panel of ovarian cancer cell lines. Finally, the feasibility of detecting submillimeter ovarian cancer cell peritoneal metastases in vivo was tested through the intravenous injection of GE137 into mice with tumor xenografts. RESULTS Using optical imaging it was possible to detect c‐Met expression in submillimeter peritoneal metastases that were freshly excised from a human high‐grade serous ovarian cancer. GE137 selectively bound to the c‐Met tyrosine kinase without activating survival signaling pathways (AKT or extracellular signal‐regulated kinase phosphorylation) downstream of c‐Met. GE137 specifically accumulated in SKOv3 ovarian cancer cells expressing c‐Met via clathrin‐mediated endocytosis and emitted a fluorescent signal that lasted for at least 8 hours in tumor xenografts in vivo with a sustained high signal‐to‐noise ratio. CONCLUSIONS Our results suggest that intraoperative optical imaging could provide a new paradigm for selecting cancer patients for appropriate targeted therapies, particularly after initial chemotherapy. Cancer 2015;121:202–13. © 2014 American Cancer Society .