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dc.contributor.authorXie, B
dc.contributor.authorTomaszewski, MR
dc.contributor.authorNeves, A
dc.contributor.authorRos, S
dc.contributor.authorHu, D
dc.contributor.authorMcGuire, S
dc.contributor.authorMullins, S
dc.contributor.authorTice, D
dc.contributor.authorSainson, R
dc.contributor.authorBohndiek, S
dc.contributor.authorWilkinson, R
dc.contributor.authorBrindle, KM
dc.date.accessioned2017-09-29T11:14:13Z
dc.date.available2017-09-29T11:14:13Z
dc.date.issued2017-11-15
dc.identifier.issn1078-0432
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/267443
dc.description.abstractPurpose: The development of new treatments and their deployment in the clinic may be assisted by imaging methods that allow an early assessment of treatment response in individual patients. The C2A domain of Synaptotagmin-I (C2Am), which binds to the phosphatidylserine (PS) exposed by apoptotic and necrotic cells, has been developed as an imaging probe for detecting cell death. Multispectral optoacoustic tomography (MSOT) is a real-time and clinically applicable imaging modality that was used here with a near infrared (NIR) fluorophore-labeled C2Am to image tumor cell death in mice treated with a TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) agonist and with 5-fluorouracil (5-FU).<br /><br />Experimental Design: C2Am was labeled with a near infrared (NIR) fluorophore and injected intravenously into mice bearing human colorectal TRAIL-sensitive Colo205 and TRAIL-resistant HT-29 xenografts that had been treated with a potent agonist of TRAILR2 and in Colo205 tumors treated with 5-FU.<br /><br />Results: Three dimensional MSOT images of probe distribution showed development of tumor contrast within 3 h of probe administration and a signal-to-background ratio in regions containing dead cells of >10 after 24 h. A site-directed mutant of C2Am that is inactive in PS binding showed negligible binding. Tumor retention of the active probe was strongly correlated (R2=0.97, P value<0.01) with a marker of apoptotic cell death measured in histological sections obtained post mortem.<br /><br />Conclusions: The rapid development of relatively high levels of contrast suggests that NIR fluorophore-labeled C2Am could be a useful optoacoustic imaging probe for detecting early therapy-induced tumor cell death in the clinic.
dc.description.sponsorshipThe work was supported by a Cancer Research UK Programme grant (17242) and a Project grant from MedImmune to KMB and by the CRUK-EPSRC Imaging Centre in Cambridge and Manchester (16465).
dc.publisherAmerican Association for Cancer Research
dc.subjecttumor
dc.subjectcell death
dc.subjectTRAIL
dc.subjectoptoacoustic imaging
dc.titleOptoacoustic detection of early therapy-induced tumor cell death using a targeted imaging agent
dc.typeArticle
prism.publicationNameClinical Cancer Research
dc.identifier.doi10.17863/CAM.12009
dcterms.dateAccepted2017-08-11
rioxxterms.versionofrecord10.1158/1078-0432.CCR-17-1029
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-08-11
dc.contributor.orcidTomaszewski, Michal [0000-0002-3194-9492]
dc.contributor.orcidNeves, André [0000-0003-2740-5166]
dc.contributor.orcidBohndiek, Sarah [0000-0003-0371-8635]
dc.contributor.orcidBrindle, Kevin [0000-0003-3883-6287]
dc.identifier.eissn1557-3265
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research UK (CB4100)
cam.issuedOnline2017-08-18
datacite.issupplementedby.doi10.17863/CAM.13025
rioxxterms.freetoread.startdate2018-08-18


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