Thiago Barboza1, Tainá Gomes2, Daniella M Mizurini3, Robson Q Monteiro3, Sandra König4, Ivo M B Francischetti5, Paula V P Signoretti6, Isalira P Ramos7, Bianca Gutfilen1, Sergio A L Souza8. 1. 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. 2. 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. 3. Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. 4. Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. 5. Vector Biology Section, Laboratory of Malaria and Vector Research, National Institutes of Health, Bethesda, MD, USA. 6. 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. 7. Laboratório de Cardiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. 8. 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.
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.
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.
Authors: Aline R M Lobba; Miryam Paola Alvarez-Flores; Melissa Regina Fessel; Marcus Vinicius Buri; Douglas S Oliveira; Renata N Gomes; Priscila S Cunegundes; Carlos DeOcesano-Pereira; Victor D Cinel; Ana M Chudzinski-Tavassi Journal: Front Mol Biosci Date: 2022-08-16
Authors: Shahid Karim; Deepak Kumar; Steve Adamson; Joshua R Ennen; Carl P Qualls; José M C Ribeiro Journal: Ticks Tick Borne Dis Date: 2020-09-25 Impact factor: 3.744