Cited by 140Cancer, Hypoxia, and MetabolismAdvanced NMR Techniques and ApplicationsAdvanced MRI Techniques and Applications

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Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1

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Granlund, Kristin L., Tee, Sui-Seng, Vargas, Hebert A., Lyashchenko, Serge K., Reznik, Ed, Fine, Samson, Laudone, Vincent, Eastham, James A., Touijer, Karim A., Reuter, Victor E., Gonen, Mithat, Sosa, Ramon E., Nicholson, Duane, Guo, YanWei W., Chen, Albert P., Tropp, James, Robb, Fraser, Hricak, Hedvig, Keshari, Kayvan R.·2020·Cell Metabolism

DOI 10.1016/j.cmet.2019.08.024PMC PMC6949382

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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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Authors: Granlund, K. L., Tee, S.-S., Vargas, H. A., Lyashchenko, S. K., Reznik, E., Fine, S., Laudone, V., Eastham, J. A., Touijer, K. A., Reuter, V. E., Gonen, M., Sosa, R. E., Nicholson, D., Guo, Y. W., Chen, A. P., Tropp, J., Robb, F., Hricak, H., & Keshari, K. R.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Corresponding author: Keshari, Kayvan R.
ORCID: Granlund, Kristin L.
Tee, Sui-Seng
Vargas, Hebert A.
Reznik, Ed
Fine, Samson
Laudone, Vincent
Reuter, Victor E.
Guo, YanWei W.
Chen, Albert P.
Robb, Fraser
Hricak, Hedvig
Keshari, Kayvan R.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2020-01
Volume: 31
Issue: 1
Pages: 105-114.e3
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2019.08.024
PMC: PMC6949382
OpenAlex: W2975630107
Cited by: 138
References: 57
Citations by year: 2026: 11 · 2025: 12 · 2024: 21 · 2023: 25 · 2022: 19 · 2021: 32 · 2020: 18
FWCI: 5.46
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 372 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords: hyperpolarized MRI, prostate cancer, pyruvate metabolism, lactate, MCT1, Gleason grade, tumor metabolic imaging, PTEN loss, actionable mutations, tumor grade
MeSH terms: RNA-Seq, Monocarboxylate Transport Protein 1, Aged, Carbon Isotopes, Humans, Kinetics, Magnetic Resonance Imaging, Male, Middle Aged, Prostatic Neoplasms, Reproducibility of Results, Pyruvic Acid, Lactic Acid, Monocarboxylic Acid Transporters, Symporters, PTEN Phosphohydrolase, Neoplasm Grading

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Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1

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