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dc.contributor.authorSerrao, Eva Men
dc.contributor.authorKettunen, Mikko Ien
dc.contributor.authorRodrigues, Tiago Ben
dc.contributor.authorDzien, Piotren
dc.contributor.authorWright, Alanen
dc.contributor.authorGopinathan, Aarthien
dc.contributor.authorGallagher, Ferdiaen
dc.contributor.authorLewis, David Yen
dc.contributor.authorFrese, Kristopher Ken
dc.contributor.authorAlmeida, Jaimeen
dc.contributor.authorHowat, William Jen
dc.contributor.authorTuveson, David Aen
dc.contributor.authorBrindle, Kevinen
dc.identifier.citationSerrao et al. Gut (2016), 65:3, pp. 465-475. doi:10.1136/gutjnl-2015-310114en
dc.description.abstractObjectives: Pancreatic cancer (PCa) is treatable by surgery when detected at an early stage. Non-invasive imaging methods able to detect both established tumors and their precursor lesions are needed to select patients for surgery. We investigated here whether pancreatic preneoplasia could be detected prior to the development of invasive cancers in genetically engineered mouse models of PCa using metabolic imaging. Design: The concentrations of alanine and lactate and the activities of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) were measured in extracts prepared from the pancreas of animals at different stages of disease progression; from pancreatitis, through tissue with predominantly low-grade and then high-grade pancreatic intraepithelial neoplasia (PanIN) and then tumor. ¹³C magnetic resonance spectroscopic imaging (¹³C-MRSI) was used to measure non-invasively changes in ¹³C labeling of alanine and lactate with disease progression, following injection of hyperpolarized [1-¹³C]pyruvate. Results: Progressive decreases in the alanine/lactate concentration ratio and ALT/LDH activity ratio with disease progression were accompanied by a corresponding decrease in the [1-¹³C]alanine/[1-¹³C]lactate signal ratio observed in ¹³C-MRSI images of the pancreas. Conclusion: Metabolic imaging with hyperpolarized [1-¹³C]pyruvate enables detection and monitoring of the progression of PCa precursor lesions. Translation of this magnetic resonance imaging technique to the clinic has the potential to improve the management of patients at high-risk of developing PCa.
dc.description.sponsorshipThe work was supported by a Cancer Research UK Programme grant (17242) to K.M.B.. E.M.S. is a recipient of a fellowship from the European Union Seventh Framework Programme (FP7/2007-2013) under the Marie Curie Initial Training Network METAFLUX (project number 264780). T.B.R. is a recipient of an Intra- European Marie Curie (FP7-PEOPLE-2009-IEF, Imaging Lymphoma) fellowship and a Long-term European Molecular Biology Organization (EMBO-ALT-1145-2009) fellowship. E.M.S. and J.A. acknowledge the educational support of Programme for Advanced Medical Education from Calouste Gulbenkian Foundation, Champalimaud Foundation, Ministerio de Saude and Fundacao para a Ciencia e Tecnologia, Portugal. The polarizer and related materials were provided by GE Healthcare. The polarimeter was provided by NIHR Cambridge Biomedical Centre. The laboratory is a member of and receives support from the Cancer Research UK & Engineering and Physical Science Research Council Cancer Imaging Center in Cambridge and Manchester. The authors would also like to acknowledge Dr. Judit Espana, Dr. Athena Matakidou, Dr. Madhu Basetti, Dr. Jose Sandoval and Sarah McGuire for their help with experiments as well as the Tumor Models Core of Cancer Research UK-Cambridge Institute.
dc.publisherBMJ Group
dc.rightsAttribution 2.0 UK: England & Wales
dc.subjectpancreatic canceren
dc.titleMRI with hyperpolarised [1-¹³C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse modelen
dc.title.alternativeMagnetic resonance imaging with hyperpolarized [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model
dc.description.versionThis is the final version of the article. It first appeared from BMJ Group via
dc.rioxxterms.funderEU FP7
dc.contributor.orcidWright, Alan [0000-0002-4577-5681]
dc.contributor.orcidGallagher, Ferdia [0000-0003-4784-5230]
dc.contributor.orcidBrindle, Kevin [0000-0003-3883-6287]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (16465)
pubs.funder-project-idCancer Research UK (CB4100)
pubs.funder-project-idCancer Research UK (C14303_do not transfer)
pubs.funder-project-idCancer Research UK (16628)

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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales