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dc.contributor.authorTurnock, Sen_US
dc.contributor.authorTurton, DRen_US
dc.contributor.authorMartins, CDen_US
dc.contributor.authorChesler, Len_US
dc.contributor.authorWilson, TCen_US
dc.contributor.authorGouverneur, Ven_US
dc.contributor.authorSmith, Gen_US
dc.contributor.authorKramer-Marek, Gen_US
dc.date.accessioned2021-01-27T16:27:17Z
dc.date.issued2020-12
dc.identifier.citationScientific reports, 2020, 10 (1), pp. 20918 - ?
dc.identifier.issn2045-2322
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4323
dc.identifier.eissn2045-2322
dc.identifier.doi10.1038/s41598-020-77788-3
dc.description.abstractTargeted radiotherapy with 131 I-mIBG, a substrate of the human norepinephrine transporter (NET-1), shows promising responses in heavily pre-treated neuroblastoma (NB) patients. Combinatorial approaches that enhance 131 I-mIBG tumour uptake are of substantial clinical interest but biomarkers of response are needed. Here, we investigate the potential of 18 F-mFBG, a positron emission tomography (PET) analogue of the 123 I-mIBG radiotracer, to quantify NET-1 expression levels in mouse models of NB following treatment with AZD2014, a dual mTOR inhibitor. The response to AZD2014 treatment was evaluated in MYCN amplified NB cell lines (Kelly and SK-N-BE(2)C) by Western blot (WB) and immunohistochemistry. PET quantification of 18 F-mFBG uptake post-treatment in vivo was performed, and data correlated with NET-1 protein levels measured ex vivo. Following 72 h AZD2014 treatment, in vitro WB analysis indicated decreased mTOR signalling and enhanced NET-1 expression in both cell lines, and 18 F-mFBG revealed a concentration-dependent increase in NET-1 function. AZD2014 treatment failed however to inhibit mTOR signalling in vivo and did not significantly modulate intratumoural NET-1 activity. Image analysis of 18 F-mFBG PET data showed correlation to tumour NET-1 protein expression, while further studies are needed to elucidate whether NET-1 upregulation induced by blocking mTOR might be a useful adjunct to 131 I-mIBG therapy.
dc.formatElectronic
dc.format.extent20918 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.title<sup>18</sup>F-meta-fluorobenzylguanidine (<sup>18</sup>F-mFBG) to monitor changes in norepinephrine transporter expression in response to therapeutic intervention in neuroblastoma models.
dc.typeJournal Article
dcterms.dateAccepted2020-11-13
rioxxterms.versionofrecord10.1038/s41598-020-77788-3
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfScientific reports
pubs.issue1
pubs.notesNot known
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Preclinical Molecular Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Preclinical Molecular Imaging
pubs.publication-statusPublished
pubs.volume10
pubs.embargo.termsNot known
icr.researchteamPaediatric Solid Tumour Biology and Therapeuticsen_US
icr.researchteamPreclinical Molecular Imagingen_US
dc.contributor.icrauthorKramer-Marek, Gabrielaen
dc.contributor.icrauthorChesler, Louisen


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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0