dc.contributor.author | Turnock, S | |
dc.contributor.author | Turton, DR | |
dc.contributor.author | Martins, CD | |
dc.contributor.author | Chesler, L | |
dc.contributor.author | Wilson, TC | |
dc.contributor.author | Gouverneur, V | |
dc.contributor.author | Smith, G | |
dc.contributor.author | Kramer-Marek, G | |
dc.date.accessioned | 2021-01-27T16:27:17Z | |
dc.date.issued | 2020-12-01 | |
dc.identifier.citation | Scientific reports, 2020, 10 (1), pp. 20918 - ? | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4323 | |
dc.identifier.eissn | 2045-2322 | |
dc.identifier.doi | 10.1038/s41598-020-77788-3 | |
dc.description.abstract | Targeted radiotherapy with 131I-mIBG, a substrate of the human norepinephrine transporter (NET-1), shows promising responses in heavily pre-treated neuroblastoma (NB) patients. Combinatorial approaches that enhance 131I-mIBG tumour uptake are of substantial clinical interest but biomarkers of response are needed. Here, we investigate the potential of 18F-mFBG, a positron emission tomography (PET) analogue of the 123I-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 18F-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 18F-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 18F-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 131I-mIBG therapy. | |
dc.format | Electronic | |
dc.format.extent | 20918 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | 18F-meta-fluorobenzylguanidine (18F-mFBG) to monitor changes in norepinephrine transporter expression in response to therapeutic intervention in neuroblastoma models. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-11-13 | |
rioxxterms.versionofrecord | 10.1038/s41598-020-77788-3 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-12 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Scientific reports | |
pubs.issue | 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 10 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Paediatric Solid Tumour Biology and Therapeutics | |
icr.researchteam | Preclinical Molecular Imaging | |
dc.contributor.icrauthor | Turnock, Stephen | |
dc.contributor.icrauthor | Chesler, Louis | |
dc.contributor.icrauthor | Smith, Graham | |
dc.contributor.icrauthor | Kramer-Marek, Gabriela | |