Abstract LB-164: Towards operative in vivo fluorescence imaging of c-Met proto-oncogene for personalization of therapy in ovarian cancer

Abstract

The recent recognition of the scale of the problem of tumour heterogeneity has made it clear that standard biomarker testing of a single macroscopic disease sites is unlikely to be sufficient. A focus on examining global biomarker expression or activity is needed for appropriate selection of targeted therapies. A particular attention to microscopic residual chemotherapy-residual disease (MRCD) would ensure appropriate targeting of chemotherapy resistance. However, the techniques for global assessment of biomarkers in patients with MRCD have not established. Using an in-house developed fluorescent imaging device we show that it is possible to identify global c-Met expression in submillimeter peritoneal metastases that were freshly excised from a human high-grade serous ovarian cancer. We evaluated a modified Cy5-tagged peptide (GE137) that selectively binds to the c-Met tyrosine kinase and demonstrated the feasibility of detecting submillimeter ovarian cancer cell peritoneal metastases in vivo following intravenous injection of this peptide. GE137 specifically accumulated in cells that express c-Met via clathrin-mediated endocytosis and emitted a fluorescent signal that lasted for at least 8 hours in tumour xenografts in vivo with a sustained high signal to noise ratio. Thus, intraoperative optical imaging could provide a new paradigm for selecting cancer patients with MRCD for appropriate targeted therapies following initial chemotherapy. Citation Format: Shujuan Liu, Yong Zheng, Davide Volpi, Muna El-Kasti, Daniel Klotz, Iain Tullis, Andrea Henricks, Leticia Campo, Kevin Myers, Alex Laios, Peter Thomas, Tony Ng, Sunanda Dhar, Christian Becker, Borivoj Vojnovic, Ahmed A. Ahmed. Towards operative in vivo fluorescence imaging of c-Met proto-oncogene for personalization of therapy in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-164. doi:10.1158/1538-7445.AM2014-LB-164