Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1.
Cell Metab
; 31(1): 105-114.e3, 2020 01 07.
Article
em En
| MEDLINE
| ID: mdl-31564440
ABSTRACT
Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients. Furthermore, we show that lactate increases with Gleason grade. RNA sequencing data demonstrate a significant increase in the predominant pyruvate uptake transporter, monocarboxylate transporter 1. Increased protein expression was also observed in regions of high lactate signal, implicating it as the driver of lactate signal in vivo. Targeted DNA sequencing for actionable mutations revealed the highest lactate occurred in patients with PTEN loss. This work identifies a potential link between actionable genomic alterations and metabolic information derived from hyperpolarized pyruvate MRI.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Imageamento por Ressonância Magnética
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Ácido Láctico
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Ácido Pirúvico
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Transportadores de Ácidos Monocarboxílicos
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Simportadores
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article