Full Length Article99mTc-ixolaris targets glioblastoma-associated tissue factor: In vitro and pre-clinical applications

•Tissue factor is commonly overexpressed in aggressive tumors including glioma grade IV (glioblastoma)•Tissue factor is a potential target for imaging TF-expressing tumors•Radiolabeling of ixolaris with Technetium-99 m (99mTc) does not interfere with its inhibitory effect towards tissue factor•99mTc-ixolaris recognizes tissue factor in a mice model of glioblastoma

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.