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dc.contributor.authorCasey, Ruthen
dc.contributor.authorMcLean, Maryen
dc.contributor.authorMadhu, Basettien
dc.contributor.authorChallis, Benjamin Gen
dc.contributor.authorten Hoopen, Rogieren
dc.contributor.authorRoberts, Thomasen
dc.contributor.authorClark, Graemeen
dc.contributor.authorPitfield, Deborahen
dc.contributor.authorSimpson, Helen Len
dc.contributor.authorBulusu, Venkata Ren
dc.contributor.authorAllinson, Kierenen
dc.contributor.authorHapperfield, Lisaen
dc.contributor.authorPark, Soo-Mien
dc.contributor.authorMarker, Alisonen
dc.contributor.authorGiger, Olivieren
dc.contributor.authorMaher, Eamonnen
dc.contributor.authorGallagher, Ferdiaen
dc.date.accessioned2018-07-02T13:45:04Z
dc.date.available2018-07-02T13:45:04Z
dc.date.issued2018-11en
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/277714
dc.description.abstractPurpose Mutations in the mitochondrial enzyme succinate dehydrogenase (SDH) subunit genes are associated with a wide spectrum of tumors, including pheochromocytomas and paragangliomas, GI stromal tumors, renal cell carcinomas, and pituitary adenomas. SDH-related tumorigenesis is believed to be secondary to accumulation of the oncometabolite succinate. Our aim was to investigate the potential clinical applications of proton-1 magnetic resonance spectroscopy (1H-MRS) in a range of suspected SDH-related tumors. Patients and Methods Fifteen patients were recruited to this study. Respiratory-gated single-voxel 1H-MRS was performed at 3T to quantify the content of succinate at 2.4 ppm and choline at 3.22 ppm. Results A succinate peak was seen in six patients, all of whom had germ line SDHx mutations or loss of SDHB by immunohistochemistry. Succinate peaks were also detected in two patients with metastatic wild-type GI stromal tumors and no detectable germ line SDHx mutations but with somatic epimutations in SDHC. Three patients without tumor succinate peaks retained SDHB expression, consistent with SDH functionality. In six patients with borderline or absent peaks, technical difficulties such as motion artifact rendered 1H-MRS difficult to interpret. Sequential imaging in a patient with a metastatic abdominal paraganglioma demonstrated loss of the succinate peak after four cycles of [177Lu]DOTATATE, with a corresponding biochemical response in normetanephrine. Conclusion This study has demonstrated the translation into clinical practice of in vivo metabolomic analysis using 1H-MRS in patients with SDH-deficient tumors. Potential applications include noninvasive diagnosis and disease stratification, as well as monitoring of tumor response to targeted treatments.
dc.languageenen
dc.publisherAmerican Society of Clinical Oncology
dc.titleTranslating In Vivo Metabolomic Analysis of Succinate Dehydrogenase–Deficient Tumors Into Clinical Utilityen
dc.typeArticle
prism.endingPage12
prism.issueIdentifier2en
prism.publicationDate2018en
prism.publicationNameJCO Precision Oncologyen
prism.startingPage1
dc.identifier.doi10.17863/CAM.25051
dcterms.dateAccepted2018-01-24en
rioxxterms.versionofrecord10.1200/po.17.00191en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-11en
dc.contributor.orcidMcLean, Mary [0000-0002-3752-0179]
dc.contributor.orcidGiger, Olivier [0000-0003-3390-6397]
dc.contributor.orcidMaher, Eamonn [0000-0002-6226-6918]
dc.contributor.orcidGallagher, Ferdia [0000-0003-4784-5230]
dc.identifier.eissn2473-4284
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
pubs.funder-project-idHealth Research Board (via National University of Ireland, Galway) (unknown)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (C14303_do not transfer)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0616-10035)
pubs.funder-project-idGIST Support UK (GSUKRC01)
pubs.funder-project-idEuropean Research Council (323004)
rioxxterms.freetoread.startdate2019-03-29


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