99mTc-ixolaris targets glioblastoma-associated tissue factor: In vitro and pre-clinical applications

Abstract

BackgroundThe clotting initiator protein tissue factor (TF) has recently been described as a potential target that can be exploited to image aggressive tumors. Ixolaris is a specific TF inhibitor that blocks tumor cell procoagulant activity and tumor growth. ObjectiveHerein we evaluated the ability of 99mTc-ixolaris to target tumor-derived TF using an orthotopic glioblastoma (GBM) model in mice. MethodsThe right forebrains of Swiss mice were stereotactically inoculated with U87-MG human GBM cells. Histological and immunohistochemical analyses were performed on the resulting tumors after 35–45 days. The biodistribution of 99mTc-ixolaris was evaluated by semi-quantitative whole-body scintigraphy and a quantitative analysis of radioactivity in isolated organs. ResultsNo 99mTc-ixolaris uptake was observed in brain of tumor-free mice, independently of the integrity of brain–blood barrier. In contrast, the presence of TF-expressing brain tumor masses determined a significant 99mTc-ixolaris uptake. Conclusion99mTc-ixolaris recognized TF-expressing GBM cells in vivo. Given the proposed role of TF in tumor progression, 99mTc-ixolaris is a promising radiopharmaceutical agent for quantifying cancer-associated TF in aggressive tumors, including GBM.