Cancers (Jan 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
- Stephan Ursprung,
- Ramona Woitek,
- Mary A. McLean,
- Andrew N. Priest,
- Mireia Crispin-Ortuzar,
- Cara R. Brodie,
- Andrew B. Gill,
- Marcel Gehrung,
- Lucian Beer,
- Antony C. P. Riddick,
- Johanna Field-Rayner,
- James T. Grist,
- Surrin S. Deen,
- Frank Riemer,
- Joshua D. Kaggie,
- Fulvio Zaccagna,
- Joao A. G. Duarte,
- Matthew J. Locke,
- Amy Frary,
- Tevita F. Aho,
- James N. Armitage,
- Ruth Casey,
- Iosif A. Mendichovszky,
- Sarah J. Welsh,
- Tristan Barrett,
- Martin J. Graves,
- Tim Eisen,
- Thomas J. Mitchell,
- Anne Y. Warren,
- Kevin M. Brindle,
- Evis Sala,
- Grant D. Stewart,
- Ferdia A. Gallagher
Affiliations
- Stephan Ursprung
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Ramona Woitek
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Mary A. McLean
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Andrew N. Priest
- Department of Radiology, University of Cambridge, Cambridge CB2 0QQ, UK
- Mireia Crispin-Ortuzar
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Cara R. Brodie
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Andrew B. Gill
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Marcel Gehrung
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Lucian Beer
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Antony C. P. Riddick
- Department of Urology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
- Johanna Field-Rayner
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- James T. Grist
- Department of Radiology, University of Cambridge, Cambridge CB2 0QQ, UK
- Surrin S. Deen
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Frank Riemer
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Joshua D. Kaggie
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Fulvio Zaccagna
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Joao A. G. Duarte
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Matthew J. Locke
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Amy Frary
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Tevita F. Aho
- Department of Urology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
- James N. Armitage
- Department of Urology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
- Ruth Casey
- Department of Endocrinology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
- Iosif A. Mendichovszky
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Sarah J. Welsh
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Tristan Barrett
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Martin J. Graves
- Department of Radiology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
- Tim Eisen
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Thomas J. Mitchell
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Anne Y. Warren
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Kevin M. Brindle
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Evis Sala
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Grant D. Stewart
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- Ferdia A. Gallagher
- Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0QQ, UK
- DOI
- https://doi.org/10.3390/cancers14020335
- Journal volume & issue
-
Vol. 14,
no. 2
p. 335
Abstract
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 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.
Keywords
- cancer metabolism
- hyperpolarized <sup>13</sup>C magnetic resonance imaging
- monocarboxylate transporter
- renal cell carcinoma
