title: (99m)Tc-ixolaris targets glioblastoma-associated tissue factor: in vitro and pre-clinical applications.
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.
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Laboratório de Marcação de Células e Moléculas, Departamento de Radiologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Barboza
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil; Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Tainá
authors.initials: T
authors.lastname: Gomes
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Daniella M
authors.initials: DM
authors.lastname: Mizurini
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Robson Q
authors.initials: RQ
authors.lastname: Monteiro
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Sandra
authors.initials: S
authors.lastname: König
authors.affiliation: Vector Biology Section, Laboratory of Malaria and Vector Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ivo M B
authors.initials: IM
authors.lastname: Francischetti
authors.affiliation: Laboratório de Físico-Química Biológica Aída Hassón Voloch e Laboratório Intermediário de Biomembranas, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Paula V P
authors.initials: PV
authors.lastname: Signoretti
authors.affiliation: Laboratório de Cardiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Isalira P
authors.initials: IP
authors.lastname: Ramos
authors.affiliation: Laboratório de Marcação de Células e Moléculas, Departamento de Radiologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Gutfilen
authors.affiliation: Laboratório de Marcação de Células e Moléculas, Departamento de Radiologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. Electronic address: sergioalsouza@gmail.com.
authors.forename: Sergio A L
authors.initials: SA
authors.lastname: Souza
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012471:Salivary Proteins and Peptides / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D013667:Technetium / Q000493:pharmacokinetics*; D013925:Thromboplastin / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; C455900:Ixolaris protein, Ixodes scapularis; D019275:Radiopharmaceuticals; D012471:Salivary Proteins and Peptides; D013667:Technetium; D013925:Thromboplastin
keywords: Glioblastoma; Ixolaris; Technetium-99m; Tissue factor