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
Authors
Woitek, R
Priest, AN
Crispin-Ortuzar, M
Brodie, CR
Gehrung, M
Beer, L
Riddick, ACP
Field-Rayner, J
Grist, JT
Deen, SS
Riemer, F
Zaccagna, F
Duarte, JAG
Locke, MJ
Aho, TF
Armitage, JN
Casey, R
Mendichovszky, IA
Mitchell, TJ
Publication Date
2022-01-11Journal Title
Cancers
ISSN
2072-6694
Publisher
MDPI AG
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Ursprung, S., Woitek, R., McLean, M., Priest, A., Crispin-Ortuzar, M., Brodie, C., Gill, A., et al. (2022). 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. Cancers https://doi.org/10.3390/cancers14020335
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>
Sponsorship
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research UK (C12912/A27150)
Wellcome Trust (095962/Z/11/Z)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cancer Research UK (A25117)
Identifiers
External DOI: https://doi.org/10.3390/cancers14020335
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332457
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