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dc.contributor.authorUrsprung, Stephan
dc.contributor.authorWoitek, Ramona
dc.contributor.authorMcLean, Mary A
dc.contributor.authorPriest, Andrew N
dc.contributor.authorCrispin-Ortuzar, Mireia
dc.contributor.authorBrodie, Cara R
dc.contributor.authorGill, Andrew B
dc.contributor.authorGehrung, Marcel
dc.contributor.authorBeer, Lucian
dc.contributor.authorRiddick, Antony CP
dc.contributor.authorField-Rayner, Johanna
dc.contributor.authorGrist, James T
dc.contributor.authorDeen, Surrin S
dc.contributor.authorRiemer, Frank
dc.contributor.authorKaggie, Joshua D
dc.contributor.authorZaccagna, Fulvio
dc.contributor.authorDuarte, Joao AG
dc.contributor.authorLocke, Matthew J
dc.contributor.authorFrary, Amy
dc.contributor.authorAho, Tevita F
dc.contributor.authorArmitage, James N
dc.contributor.authorCasey, Ruth
dc.contributor.authorMendichovszky, Iosif A
dc.contributor.authorWelsh, Sarah J
dc.contributor.authorBarrett, Tristan
dc.contributor.authorGraves, Martin J
dc.contributor.authorEisen, Tim
dc.contributor.authorMitchell, Thomas J
dc.contributor.authorWarren, Anne Y
dc.contributor.authorBrindle, Kevin M
dc.contributor.authorSala, Evis
dc.contributor.authorStewart, Grant D
dc.contributor.authorGallagher, Ferdia A
dc.description.abstractDifferentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.sourcenlmid: 101526829
dc.sourceessn: 2072-6694
dc.subjectRenal cell carcinoma
dc.subjectMonocarboxylate transporter
dc.subjectCancer Metabolism
dc.subjectHyperpolarized 13c Magnetic Resonance Imaging
dc.titleHyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.
prism.publicationNameCancers (Basel)
dc.contributor.orcidUrsprung, Stephan [0000-0003-2476-178X]
dc.contributor.orcidPriest, Andrew N [0000-0002-9771-4290]
dc.contributor.orcidGill, Andrew B [0000-0002-9287-9563]
dc.contributor.orcidBeer, Lucian [0000-0003-4388-7580]
dc.contributor.orcidDeen, Surrin S [0000-0002-6206-7337]
dc.contributor.orcidRiemer, Frank [0000-0002-3805-5221]
dc.contributor.orcidKaggie, Joshua D [0000-0001-6706-3442]
dc.contributor.orcidZaccagna, Fulvio [0000-0001-6838-9532]
dc.contributor.orcidWelsh, Sarah J [0000-0001-5690-2677]
dc.contributor.orcidEisen, Tim [0000-0001-9663-4873]
dc.contributor.orcidBrindle, Kevin M [0000-0003-3883-6287]
dc.contributor.orcidStewart, Grant D [0000-0003-3188-9140]
dc.contributor.orcidGallagher, Ferdia A [0000-0003-4784-5230]
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research UK (C12912/A27150)
pubs.funder-project-idWellcome Trust (095962/Z/11/Z)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idCancer Research UK (A25117)
pubs.funder-project-idMRC (MR/T024097/1)
pubs.funder-project-idEPSRC (EP/T017961/1)

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