(99m)Tc-ixolaris targets glioblastoma-associated tissue factor: in vitro and pre-clinical applications.


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.

DOI: 10.1016/j.thromres.2015.05.032

Cite this paper

@article{Barboza201599mTcixolarisTG, title={(99m)Tc-ixolaris targets glioblastoma-associated tissue factor: in vitro and pre-clinical applications.}, author={Thiago Barboza and Tain{\'a} Gomes and Daniella M . Mizurini and Robson Queiroz Monteiro and Sandra K{\"{o}nig and Ivo M B Francischetti and Paula V P Signoretti and Isalira P Ramos and Bianca Gutfilen and Sergio Augusto Lopes Souza}, journal={Thrombosis research}, year={2015}, volume={136 2}, pages={432-9} }