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(99m)Tc-ixolaris targets glioblastoma-associated tissue factor: in vitro and pre-clinical applications
Thiago Barboza1, Tainá Gomes2, Daniella M Mizurini3
1Laboratório de Marcação de Células e Moléculas, Departamento de Radiologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
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.
Insights
Tc-ixolaris effectively targets tissue factor (TF) in glioblastoma (GBM) tumors. This radiopharmaceutical shows promise for imaging aggressive cancers by detecting TF-expressing cells in vivo.
Area of Science:
- Oncology
- Radiopharmaceuticals
- Molecular Imaging
Background:
- Tissue factor (TF) is a protein implicated in aggressive tumor progression and is a potential imaging target.
- Ixolaris is a TF inhibitor that reduces tumor cell procoagulant activity and growth.
Purpose of the Study:
- To assess the efficacy of (99m)Tc-ixolaris in targeting tumor-derived TF.
- To evaluate (99m)Tc-ixolaris in an orthotopic glioblastoma (GBM) mouse model.
Main Methods:
- U87-MG human GBM cells were stereotactically inoculated into the brains of Swiss mice.
- Tumor development was assessed after 35-45 days via histological and immunohistochemical analyses.
- Biodistribution of (99m)Tc-ixolaris was evaluated using whole-body scintigraphy and organ radioactivity quantification.
Main Results:
- No significant (99m)Tc-ixolaris uptake was observed in the brains of tumor-free mice.
- Tumor masses expressing TF showed significant uptake of (99m)Tc-ixolaris.
Conclusions:
- (99m)Tc-ixolaris successfully recognized TF-expressing GBM cells in vivo.
- (99m)Tc-ixolaris demonstrates potential as a radiopharmaceutical agent for quantifying cancer-associated TF in aggressive tumors like GBM.
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