Background: The 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.
Objective: Herein we evaluated the ability of (99m)Tc-ixolaris to target tumor-derived TF using an orthotopic glioblastoma (GBM) model in mice.
Methods: The 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 (99m)Tc-ixolaris was evaluated by semi-quantitative whole-body scintigraphy and a quantitative analysis of radioactivity in isolated organs.
Results: No (99m)Tc-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 (99m)Tc-ixolaris uptake.
Conclusion: (99m)Tc-ixolaris recognized TF-expressing GBM cells in vivo. Given the proposed role of TF in tumor progression, (99m)Tc-ixolaris is a promising radiopharmaceutical agent for quantifying cancer-associated TF in aggressive tumors, including GBM.
Keywords: Glioblastoma; Ixolaris; Technetium-99m; Tissue factor.
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