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Targeting the extradomain A of fibronectin allows identification of vascular resistance to antiangiogenic therapy in experimental glioma.
Acker, Güliz; Piper, Sophie Käthe; Datwyler, Anna Lena; Broggini, Thomas; Kremenetskaia, Irina; Nieminen-Kelhä, Melina; Lips, Janet; Harms, Ulrike; Mueller, Susanne; Lättig-Tünnemann, Gilla; Trachsel, Eveline; Palumbo, Alessandro; Neri, Dario; Klohs, Jan; Endres, Matthias; Vajkoczy, Peter; Harms, Christoph; Czabanka, Marcus.
Afiliación
  • Acker G; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurosurgery, Berlin, Germany.
  • Piper SK; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research, Berlin, Germany.
  • Datwyler AL; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany.
  • Broggini T; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research, Berlin, Germany.
  • Kremenetskaia I; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology and Experimental Neurology, Berlin, Germany.
  • Nieminen-Kelhä M; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurosurgery, Berlin, Germany.
  • Lips J; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurosurgery, Berlin, Germany.
  • Harms U; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurosurgery, Berlin, Germany.
  • Mueller S; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research, Berlin, Germany.
  • Lättig-Tünnemann G; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology and Experimental Neurology, Berlin, Germany.
  • Trachsel E; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research, Berlin, Germany.
  • Palumbo A; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology and Experimental Neurology, Berlin, Germany.
  • Neri D; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research, Berlin, Germany.
  • Klohs J; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology and Experimental Neurology, Berlin, Germany.
  • Endres M; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research, Berlin, Germany.
  • Vajkoczy P; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology and Experimental Neurology, Berlin, Germany.
  • Harms C; Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
  • Czabanka M; Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Oncotarget ; 9(45): 27760-27772, 2018 Jun 12.
Article en En | MEDLINE | ID: mdl-29963235
ABSTRACT

INTRODUCTION:

Clinical application of antiangiogenic therapy lacks direct visualization of therapy efficacy and vascular resistance. We aimed to establish molecular imaging during treatment with sunitinib using the fibronectin extradomain A specific small immunoprotein(SIP)-F8 in glioma.

METHODS:

Biodistribution analysis of F8-SIP-Alexa-555 was performed in SF126-glioma bearing or control mice (n = 23 and 7, respectively). Intravital microscopy(IVM) was performed on a microvascular level after 7 days (n = 5 per group) and subsequently after 6 days of sunitinib treatment (n = 4) or without (n = 2).Additionally, near infrared fluorescence(NIRF) imaging was established with F8-SIP-Alexa-750 allowing non-invasive imaging with and without antiangiogenic treatment in orthotopic tumors (n = 38 divided in 4 groups). MRI was used to determine tumor size and served as a reference for NIRF imaging.

RESULTS:

F8-SIP demonstrated a time and hemodynamic dependent tumor specific accumulation. A significantly higher vascular accumulation occurred with antiangiogenic treatment compared to untreated tumors enabling visualization of resistant tumor vessels by F8-SIP-mediated NIRF imaging. In orthotopic tumors, sunitinib reduced F8-SIP-Alexa-750 enrichment volume but not fluorescence intensity indicative of F8-SIP accumulation in fewer vessels.

CONCLUSION:

F8-SIP is highly tumor specific with time and hemodynamic dependent biodistribution. The higher vascular accumulation to remaining vessels enables molecular imaging and targeting of therapy resistant tumor vessels.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies Idioma: En Revista: Oncotarget Año: 2018 Tipo del documento: Article País de afiliación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies Idioma: En Revista: Oncotarget Año: 2018 Tipo del documento: Article País de afiliación: Alemania