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dc.contributor.authorRobinson, SPen_US
dc.contributor.authorBoult, JKRen_US
dc.contributor.authorVasudev, NSen_US
dc.contributor.authorReynolds, ARen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2018-09-13T11:01:44Z
dc.date.issued2017-08-01en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28566330en_US
dc.identifier0008-5472.CAN-17-0248en_US
dc.identifier.citationCancer Res, 2017, 77 (15), pp. 4127 - 4134en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2683
dc.identifier.eissn1538-7445en_US
dc.identifier.doi10.1158/0008-5472.CAN-17-0248en_US
dc.description.abstractAntiangiogenic therapy is efficacious in metastatic renal cell carcinoma (mRCC). However, the ability of antiangiogenic drugs to delay tumor progression and extend survival is limited, due to either innate or acquired drug resistance. Furthermore, there are currently no validated biomarkers that predict which mRCC patients will benefit from antiangiogenic therapy. Here, we exploit susceptibility contrast MRI (SC-MRI) using intravascular ultrasmall superparamagnetic iron oxide particles to quantify and evaluate tumor fractional blood volume (fBV) as a noninvasive imaging biomarker of response to the antiangiogenic drug sunitinib. We also interrogate the vascular phenotype of RCC xenografts exhibiting acquired resistance to sunitinib. SC-MRI of 786-0 xenografts prior to and 2 weeks after daily treatment with 40 mg/kg sunitinib revealed a 71% (P < 0.01) reduction in fBV in the absence of any change in tumor volume. This response was associated with significantly lower microvessel density (P < 0.01) and lower uptake of the perfusion marker Hoechst 33342 (P < 0.05). The average pretreatment tumor fBV was negatively correlated (R2 = 0.92, P < 0.0001) with sunitinib-induced changes in tumor fBV across the cohort. SC-MRI also revealed suppressed fBV in tumors that acquired resistance to sunitinib. In conclusion, SC-MRI enabled monitoring of the antiangiogenic response of 786-0 RCC xenografts to sunitinib, which revealed that pretreatment tumor fBV was found to be a predictive biomarker of subsequent reduction in tumor blood volume in response to sunitinib, and acquired resistance to sunitinib was not associated with a parallel increase in tumor blood volume. Cancer Res; 77(15); 4127-34. ©2017 AACR.en_US
dc.format.extent4127 - 4134en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAngiogenesis Inhibitorsen_US
dc.subjectAnimalsen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectCarcinoma, Renal Cellen_US
dc.subjectCell Line, Tumoren_US
dc.subjectContrast Mediaen_US
dc.subjectDextransen_US
dc.subjectDrug Resistance, Neoplasmen_US
dc.subjectFemaleen_US
dc.subjectHumansen_US
dc.subjectImage Processing, Computer-Assisteden_US
dc.subjectImmunohistochemistryen_US
dc.subjectIndolesen_US
dc.subjectKidney Neoplasmsen_US
dc.subjectMagnetic Resonance Imagingen_US
dc.subjectMagnetite Nanoparticlesen_US
dc.subjectMiceen_US
dc.subjectMice, SCIDen_US
dc.subjectMicroscopy, Fluorescenceen_US
dc.subjectPyrrolesen_US
dc.subjectSunitiniben_US
dc.subjectXenograft Model Antitumor Assaysen_US
dc.titleMonitoring the Vascular Response and Resistance to Sunitinib in Renal Cell Carcinoma In Vivo with Susceptibility Contrast MRI.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-05-22en_US
rioxxterms.versionofrecord10.1158/0008-5472.CAN-17-0248en_US
rioxxterms.licenseref.startdate2017-08-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCancer Resen_US
pubs.issue15en_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.publication-statusPublisheden_US
pubs.volume77en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamMagnetic Resonanceen_US
dc.contributor.icrauthorBoult, Jessicaen_US
dc.contributor.icrauthorRobinson, Simonen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/