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Imaging breast cancer using hyperpolarized carbon-13 MRI.

Published version
Peer-reviewed

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Authors

Gallagher, Ferdia A  ORCID logo  https://orcid.org/0000-0003-4784-5230
McLean, Mary A 
Gill, Andrew B 
Manzano Garcia, Raquel  ORCID logo  https://orcid.org/0000-0002-5124-8992

Abstract

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Description

Keywords

breast cancer, cancer metabolism, magnetic resonance imaging, metabolic imaging, Breast Neoplasms, Carbon Isotopes, Female, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, L-Lactate Dehydrogenase, Magnetic Resonance Imaging, Monocarboxylic Acid Transporters, Muscle Proteins, Pyruvic Acid, Symporters

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

117

Publisher

Proceedings of the National Academy of Sciences
Sponsorship
Cancer Research UK (C37096/A16673)
Wellcome Trust (095962/Z/11/Z)
Cancer Research UK (CB4100)
Cancer Research UK (C14303/A17197)
Cancer Research UK (17242)
Cancer Research UK (unknown)
Cancer Research Uk (None)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10067)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Cancer Research Uk (None)
Cancer Research UK (60098573)
Cancer Research UK (unknown)
Cancer Research UK (7325)
Cancer Research Uk (None)
Cambridge University Hospitals NHS Foundation Trust (CUH) (RG51913)
Cancer Research UK (CB4140)
Cancer Research UK (15580)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10090)
Cancer Research UK (A27657)
MRC (unknown)
Cancer Research UK (C96/A25177)
This work was supported by a Wellcome Trust Strategic Award, Cancer Research UK (CRUK; C8742/A18097, C19212/A16628, C19212/A911376, C197/A16465), the Austrian Science Fund (J4025-B26), the CRUK Cambridge Centre, the CRUK & Engineering and Physical Sciences Research Council (EPSRC) Cancer Imaging Centre in Cambridge and Manchester, the Mark Foundation for Cancer Research and Cancer Research UK Cambridge Centre [C9685/A25177], Addenbrooke’s Charitable Trust, the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre and Cambridge University Hospitals NHS Foundation Trust