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 99mTc-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 99mTc-ixolaris was evaluated by semi-quantitative whole-body scintigraphy and a quantitative analysis of radioactivity in isolated organs. Results No 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. Conclusion 99mTc-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.
Original language | English (US) |
---|---|
Pages (from-to) | 432-439 |
Number of pages | 8 |
Journal | Thrombosis research |
Volume | 136 |
Issue number | 2 |
DOIs | |
State | Published - Aug 1 2015 |
Externally published | Yes |
Keywords
- Glioblastoma
- Ixolaris
- Technetium-99 m
- Tissue factor
ASJC Scopus subject areas
- Hematology