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Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.

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cam.issuedOnline2018-08-16
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.contributor.orcidTomaszewski, Michal [0000-0002-3194-9492]
dc.contributor.orcidJoseph, James [0000-0001-6270-2559]
dc.contributor.orcidBohndiek, Sarah [0000-0003-0371-8635]
dc.date.accessioned2018-09-29T06:09:31Z
dc.date.available2018-09-29T06:09:31Z
dc.date.issued2018-10-15
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.identifier.doi10.17863/CAM.30315
dc.identifier.eissn1538-7445
dc.identifier.issn0008-5472
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/282952
dc.languageeng
dc.language.isoeng
dc.publisherAmerican Association for Cancer Research (AACR)
dc.publisher.urlhttp://dx.doi.org/10.1158/0008-5472.can-18-1033
dc.subjectAlgorithms
dc.subjectAnimals
dc.subjectBiomarkers, Tumor
dc.subjectCell Hypoxia
dc.subjectCell Line, Tumor
dc.subjectContrast Media
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectMice, Nude
dc.subjectNecrosis
dc.subjectNeoplasms
dc.subjectOxygen
dc.subjectPerfusion
dc.subjectPhotoacoustic Techniques
dc.subjectSoftware
dc.subjectTumor Hypoxia
dc.titleOxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.
dc.typeArticle
dcterms.dateAccepted2018-08-13
prism.endingPage5991
prism.issueIdentifier20
prism.publicationDate2018
prism.publicationNameCancer Res
prism.startingPage5980
prism.volume78
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research UK (C14303/A17197)
pubs.funder-project-idCancer Research UK (C14303/A17197)
rioxxterms.licenseref.startdate2018-10
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1158/0008-5472.CAN-18-1033

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