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dc.contributor.authorTomaszewski, Michal R
dc.contributor.authorGehrung, Marcel
dc.contributor.authorJoseph, James
dc.contributor.authorQuiros-Gonzalez, Isabel
dc.contributor.authorDisselhorst, Jonathan A
dc.contributor.authorBohndiek, Sarah E
dc.date.accessioned2018-09-29T06:09:31Z
dc.date.available2018-09-29T06:09:31Z
dc.date.issued2018-10-15
dc.identifier.issn0008-5472
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/282952
dc.description.abstractMeasuring the functional status of tumor vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatiotemporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that may overcome these challenges. By acquiring data at multiple wavelengths, OT can interrogate hemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis. We found that vascular maturity led to changes in vascular function that affected tumor perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumor and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumor hypoxia quantified ex vivo Our findings indicate that OT may offer a significant advantage for localized imaging of tumor response to vascular-targeted therapies when compared with existing clinical DCE methods.Significance: Imaging biomarkers derived from optoacoustic tomography can be used as surrogate measures of tumor perfusion and hypoxia, potentially yielding rapid, multiparametric, and noninvasive cancer staging and therapeutic response monitoring in the clinic.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5980/F1.large.jpg Cancer Res; 78(20); 5980-91. ©2018 AACR.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Association for Cancer Research (AACR)
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Nude
dc.subjectNeoplasms
dc.subjectNecrosis
dc.subjectOxygen
dc.subjectContrast Media
dc.subjectPerfusion
dc.subjectCell Hypoxia
dc.subjectAlgorithms
dc.subjectSoftware
dc.subjectPhotoacoustic Techniques
dc.subjectBiomarkers, Tumor
dc.subjectTumor Hypoxia
dc.titleOxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.
dc.typeArticle
prism.endingPage5991
prism.issueIdentifier20
prism.publicationDate2018
prism.publicationNameCancer Res
prism.startingPage5980
prism.volume78
dc.identifier.doi10.17863/CAM.30315
dcterms.dateAccepted2018-08-13
rioxxterms.versionofrecord10.1158/0008-5472.CAN-18-1033
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-10
dc.contributor.orcidTomaszewski, Michal [0000-0002-3194-9492]
dc.contributor.orcidJoseph, James [0000-0001-6270-2559]
dc.contributor.orcidBohndiek, Sarah [0000-0003-0371-8635]
dc.identifier.eissn1538-7445
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research UK (C14303/A17197)
pubs.funder-project-idCancer Research UK (C14303/A17197)
cam.issuedOnline2018-08-16
rioxxterms.freetoread.startdate2019-08-16


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