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dc.contributor.authorHeinzmann, Kathrinen
dc.contributor.authorHoness, Davina Jeanen
dc.contributor.authorLewis, David Yestinen
dc.contributor.authorSmith, Donna-Michelleen
dc.contributor.authorCawthorne, Christopheren
dc.contributor.authorKeen, Heatheren
dc.contributor.authorHeskamp, Sandraen
dc.contributor.authorSchelhaas, Sonjaen
dc.contributor.authorWitney, Timothy Howarden
dc.contributor.authorSoloviev, Dmitryen
dc.contributor.authorWilliams, Kaye Janineen
dc.contributor.authorJacobs, Andreas Hansen
dc.contributor.authorAboagye, Eric Oforien
dc.contributor.authorGriffiths, Johnen
dc.contributor.authorBrindle, Kevinen
dc.date.accessioned2016-09-20T10:29:39Z
dc.date.available2016-09-20T10:29:39Z
dc.date.issued2016-08-11en
dc.identifier.issn2191-219X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/260243
dc.description.abstract${\bf Background:}$ Recent studies have shown that 3′-deoxy-3′-[$^{18}$F] fluorothymidine ([$^{18}$F]FLT)) uptake depends on endogenous tumour thymidine concentration. The purpose of this study was to investigate tumour thymidine concentrations and whether they correlated with [$^{18}$F]FLT uptake across a broad spectrum of murine cancer models. A modified liquid chromatography-mass spectrometry (LC-MS/MS) method was used to determine endogenous thymidine concentrations in plasma and tissues of tumour-bearing and non-tumour bearing mice and rats. Thymidine concentrations were determined in 22 tumour models, including xenografts, syngeneic and spontaneous tumours, from six research centres, and a subset was compared for [$^{18}$F]FLT uptake, described by the maximum and mean tumour-to-liver uptake ratio (TTL) and SUV. ${\bf Results:}$ The LC-MS/MS method used to measure thymidine in plasma and tissue was modified to improve sensitivity and reproducibility. Thymidine concentrations determined in the plasma of 7 murine strains and one rat strain were between 0.61 ± 0.12 μM and 2.04 ± 0.64 μM, while the concentrations in 22 tumour models ranged from 0.54 ± 0.17 μM to 20.65 ± 3.65 μM. TTL at 60 min after [$^{18}$F]FLT injection, determined in 14 of the 22 tumour models, ranged from 1.07 ± 0.16 to 5.22 ± 0.83 for the maximum and 0.67 ± 0.17 to 2.10 ± 0.18 for the mean uptake. TTL did not correlate with tumour thymidine concentrations. ${\bf Conclusions:}$ Endogenous tumour thymidine concentrations alone are not predictive of [$^{18}$F]FLT uptake in murine cancer models.
dc.description.sponsorshipInnovative Medicines Initiative Joint Undertaking (EU FP7/2007-2013) (Grant ID: 115151); Cancer Research UK (Grant ID: 17242, Cancer Research UK-Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester (reference 16465), Grant ID: A11562)
dc.languageEnglishen
dc.language.isoenen
dc.publisherSpringer
dc.rightsAttribution 4.0 International*
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subject[$^{18}$F]fluorothymidineen
dc.subjectplasmaen
dc.subjecttumouren
dc.subjectthymidineen
dc.subjectpreclinical PETen
dc.titleThe relationship between endogenous thymidine concentrations and [$^{18}$F]FLT uptake in a range of preclinical tumour modelsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1186/s13550-016-0218-3en
prism.number63en
prism.publicationDate2016en
prism.publicationNameEJNMMI Researchen
prism.volume6en
dc.identifier.doi10.17863/CAM.4475
dcterms.dateAccepted2016-07-28en
rioxxterms.versionofrecord10.1186/s13550-016-0218-3en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-08-11en
dc.contributor.orcidGriffiths, John [0000-0001-7369-6836]
dc.contributor.orcidBrindle, Kevin [0000-0003-3883-6287]
dc.identifier.eissn2191-219X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (CB4110)
pubs.funder-project-idCancer Research UK (16465)
pubs.funder-project-idCancer Research UK (CB4100)
pubs.funder-project-idCancer Research UK (C14303_do not transfer)
cam.orpheus.successThu Jan 30 12:58:05 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International