Abstract B116: Imaging of primary tumor and metastases in mice using near-infrared fluorescent-labeled phosphatidylserine-targeting antibodies.

Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane that becomes exposed on tumor vascular endothelial cells and tumor cells in response to chemotherapy, irradiation and oxidative stresses in the tumor microenvironment. Binding of antibodies targeting PS on the tumor endothelial cells and tumors leads to recruitment of immune cells and engagement of the immune system to destroy tumor vasculature. The antibodies also enhance anti-tumor immunity by blocking the immunosuppressive action of PS. In Phase II trials a chimeric anti-PS antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors. In the present study, we demonstrate imaging of primary tumor and metastases using real-time, near infrared fluorescence imaging of antibodies that specifically target PS. Tumor formation, proliferation rate and location of metastases were monitored by bioluminescence imaging (BLI) and near-infrared optical imaging of PS exposure using a near infrared dye-labeled (NIR) PGN635 F(ab9)2 antibody fragment. PGN635 binds PS through the interaction of beta-2-glycoprotein 1 (2GP1) in the same manner as bavituximab binding to 2GP1 in humans. Specific co-localization of BLI and NIR-labeled PGN635 F(ab9)2 was observed in tumors compared to a NIR-labeled isotype control antibody. Chemotherapy was shown to enhance the binding of PS-targeting antibodies to both primary and metastatic tumors. These data provide a rationale to image PS expression as a way to localize primary tumors or metastases and to monitor induced PS expression during the course of chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B116.