Hyperpolarized13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma—A Proof of Principle Study
cam.depositDate | 2022-01-06 | |
cam.issuedOnline | 2022-01-11 | |
cam.orpheus.success | Tue Feb 01 19:02:38 GMT 2022 - Embargo updated | * |
datacite.ispreviousversionof.handle | https://www.repository.cam.ac.uk/handle/1810/333019 | |
dc.contributor.author | Ursprung, Stephan | |
dc.contributor.author | Woitek, R | |
dc.contributor.author | McLean, Mary | |
dc.contributor.author | Priest, AN | |
dc.contributor.author | Crispin-Ortuzar, M | |
dc.contributor.author | Brodie, CR | |
dc.contributor.author | Gill, Andrew | |
dc.contributor.author | Gehrung, M | |
dc.contributor.author | Beer, L | |
dc.contributor.author | Riddick, ACP | |
dc.contributor.author | Field-Rayner, J | |
dc.contributor.author | Grist, JT | |
dc.contributor.author | Deen, SS | |
dc.contributor.author | Riemer, F | |
dc.contributor.author | Kaggie, Joshua | |
dc.contributor.author | Zaccagna, F | |
dc.contributor.author | Duarte, JAG | |
dc.contributor.author | Locke, MJ | |
dc.contributor.author | Frary, Amy | |
dc.contributor.author | Aho, TF | |
dc.contributor.author | Armitage, JN | |
dc.contributor.author | Casey, R | |
dc.contributor.author | Mendichovszky, IA | |
dc.contributor.author | Welsh, Sarah | |
dc.contributor.author | Barrett, Tristan | |
dc.contributor.author | Graves, Martin | |
dc.contributor.author | Eisen, Tim | |
dc.contributor.author | Mitchell, TJ | |
dc.contributor.author | Warren, Anne | |
dc.contributor.author | Brindle, Kevin | |
dc.contributor.author | Sala, Evis | |
dc.contributor.author | Stewart, Grant | |
dc.contributor.author | Gallagher, Ferdia | |
dc.contributor.orcid | Ursprung, Stephan [0000-0003-2476-178X] | |
dc.contributor.orcid | McLean, Mary [0000-0002-3752-0179] | |
dc.contributor.orcid | Gill, Andrew [0000-0002-9287-9563] | |
dc.contributor.orcid | Kaggie, Joshua [0000-0001-6706-3442] | |
dc.contributor.orcid | Frary, Amy [0000-0002-4373-3517] | |
dc.contributor.orcid | Welsh, Sarah [0000-0001-5690-2677] | |
dc.contributor.orcid | Barrett, Tristan [0000-0002-1180-1474] | |
dc.contributor.orcid | Graves, Martin [0000-0003-4327-3052] | |
dc.contributor.orcid | Eisen, Tim [0000-0001-9663-4873] | |
dc.contributor.orcid | Warren, Anne [0000-0002-1170-7867] | |
dc.contributor.orcid | Brindle, Kevin [0000-0003-3883-6287] | |
dc.contributor.orcid | Sala, Evis [0000-0002-5518-9360] | |
dc.contributor.orcid | Stewart, Grant [0000-0003-3188-9140] | |
dc.contributor.orcid | Gallagher, Ferdia [0000-0003-4784-5230] | |
dc.date.accessioned | 2022-01-08T00:30:25Z | |
dc.date.available | 2022-01-08T00:30:25Z | |
dc.date.issued | 2022-01-11 | |
dc.date.updated | 2022-01-06T16:56:01Z | |
dc.description.abstract | <jats:p>Differentiating 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.</jats:p> | |
dc.identifier.doi | 10.17863/CAM.79903 | |
dc.identifier.eissn | 2072-6694 | |
dc.identifier.issn | 2072-6694 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/332457 | |
dc.language.iso | eng | |
dc.publisher | MDPI AG | |
dc.publisher.department | Department of Radiology Student | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Hyperpolarized<sup>13</sup>C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma—A Proof of Principle Study | |
dc.type | Article | |
dcterms.dateAccepted | 2022-01-06 | |
prism.publicationName | Cancers | |
pubs.funder-project-id | Cancer Research Uk (None) | |
pubs.funder-project-id | Cancer Research Uk (None) | |
pubs.funder-project-id | Cancer Research UK (C12912/A27150) | |
pubs.funder-project-id | Wellcome Trust (095962/Z/11/Z) | |
pubs.funder-project-id | Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown) | |
pubs.funder-project-id | Cancer Research UK (A25117) | |
pubs.licence-display-name | Apollo Repository Deposit Licence Agreement | |
pubs.licence-identifier | apollo-deposit-licence-2-1 | |
rioxxterms.type | Journal Article/Review | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.3390/cancers14020335 |
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