99mTc-ixolaris targets glioblastoma-associated tissue factor: In vitro and pre-clinical applications. Issue 2 (August 2015)

• Record Type: Journal Article
• Authors: Barboza, Thiago; Gomes, Tainá; Mizurini, Daniella M.; Monteiro, Robson Q.; König, Sandra; Francischetti, Ivo M.B.; Signoretti, Paula V.P.; Ramos, Isalira P.; Gutfilen, Bianca; Souza, Sergio A.L.
• Is Part Of: Thrombosis research. Volume 136:Issue 2(2015)
• Page Start: 432
• Page End: 439
• Publication Date: 2015-08
• Subjects: Ixolaris -- Glioblastoma -- Technetium-99 m -- Tissue factor; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2015.05.032
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: 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. Highlights: 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 ( 99m Tc) does not interfere with its inhibitory effect towards tissue factor 99m Tc-ixolaris recognizes tissue factor in a mice model of glioblastoma