99mTc-ixolaris targets glioblastoma-associated tissue factor: In vitro and pre-clinical applications

Thiago Barboza, Tainá Gomes, Daniella M. Mizurini, Robson Q. Monteiro, Sandra König, Ivo M.B. Francischetti, Paula V.P. Signoretti, Isalira P. Ramos, Bianca Gutfilen, Sergio A.L. Souza

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)432-439
Number of pages8
JournalThrombosis research
Volume136
Issue number2
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

Keywords

  • Glioblastoma
  • Ixolaris
  • Technetium-99 m
  • Tissue factor

ASJC Scopus subject areas

  • Hematology

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