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dc.contributor.authorRobinson, SP
dc.contributor.authorBoult, JKR
dc.contributor.authorVasudev, NS
dc.contributor.authorReynolds, AR
dc.date.accessioned2018-09-13T11:01:44Z
dc.date.issued2017-08
dc.identifier.citationCancer research, 2017, 77 (15), pp. 4127 - 4134
dc.identifier.issn0008-5472
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2683
dc.identifier.eissn1538-7445
dc.identifier.doi10.1158/0008-5472.can-17-0248
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 ( R 2 = 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 .
dc.formatPrint-Electronic
dc.format.extent4127 - 4134
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectMice, SCID
dc.subjectCarcinoma, Renal Cell
dc.subjectKidney Neoplasms
dc.subjectPyrroles
dc.subjectIndoles
dc.subjectDextrans
dc.subjectAngiogenesis Inhibitors
dc.subjectAntineoplastic Agents
dc.subjectContrast Media
dc.subjectMagnetic Resonance Imaging
dc.subjectMicroscopy, Fluorescence
dc.subjectImmunohistochemistry
dc.subjectXenograft Model Antitumor Assays
dc.subjectDrug Resistance, Neoplasm
dc.subjectImage Processing, Computer-Assisted
dc.subjectFemale
dc.subjectMagnetite Nanoparticles
dc.subjectSunitinib
dc.titleMonitoring the Vascular Response and Resistance to Sunitinib in Renal Cell Carcinoma <i>In Vivo</i> with Susceptibility Contrast MRI.
dc.typeJournal Article
dcterms.dateAccepted2017-05-22
rioxxterms.versionofrecord10.1158/0008-5472.can-17-0248
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer research
pubs.issue15
pubs.notesNo embargo
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/Pre-Clinical MRI
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/Pre-Clinical MRI
pubs.publication-statusPublished
pubs.volume77
pubs.embargo.termsNo embargo
icr.researchteamPre-Clinical MRIen_US
dc.contributor.icrauthorBoult, Jessicaen
dc.contributor.icrauthorRobinson, Simonen


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