Dataset Information
Targeting the extradomain A of fibronectin allows identification of vascular resistance to antiangiogenic therapy in experimental glioma.
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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.
SUBMITTER: Acker G
PROVIDER: S-EPMC6021244 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
Targeting the extradomain A of fibronectin allows identification of vascular resistance to antiangiogenic therapy in experimental glioma.
Oncotarget 20180612 45
<h4>Introduction</h4>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.<h4>Methods</h4>Biodistribution analysis of F8-SIP-Alexa-555 was performed in SF126-glioma bearing or control mice (<i>n</i> = 23 and 7, respectively). Intravital microscopy(IVM) was performed on a microva ...[more]
