Imaging Glioblastoma Metabolism Using Hyperpolarized [1-13C]pyruvate Demonstrates Heterogeneity in Lactate Labeling: a Proof of Principle Study
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Authors
Zaccagna, Fulvio
McLean, Mary
Grist, James
Kaggie, Josh
Mair, Richard
Riemer, Frank
Woitek, Ramona
Gill, Andrew
Deen, Surrin
Daniels, Charlie
Ursprung, Stephan
Schulte, Rolf
Allinson, Kieran
Chhabra, Anita
Laurent, Marie-Christine
Locke, Matthew
Frary, Amy
Hilborne, Sarah
Patterson, Ilse
Do Carmo, Bruno
Slough, Rhys
Wilkinson, Ian
Wason, James
Gillard, Jonathan
Matys, Tomasz
Watts, Colin
Santarius, Thomas
Graves, Martin
Jefferies, Sarah
Journal Title
Radiology
ISSN
0033-8419
Publisher
Radiological Society of North America
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Brindle, K., Zaccagna, F., McLean, M., Grist, J., Kaggie, J., Mair, R., Riemer, F., et al. Imaging Glioblastoma Metabolism Using Hyperpolarized [1-13C]pyruvate Demonstrates Heterogeneity in Lactate Labeling: a Proof of Principle Study. Radiology https://doi.org/10.17863/CAM.84933
Abstract
Abstract
Purpose
Glioblastoma (GBM) metabolism was evaluated by using hyperpolarized carbon-13 MRI (HP 13C MRI) to monitor exchange of hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate.
Methods
In this prospective study, seven treatment-naïve patients (mean age, 60 ± [standard deviation] 11 years; 5 men) with GBM were imaged at 3T using a dual-tuned 13C/1H head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP) and in healthy volunteers, using paired/un-paired t-tests and Wilcoxon signed rank test. Spearman’s rho correlation coefficient was used to correlate metabolite labeling with LDH-A expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons.
Results
The bicarbonate/pyruvate (BP) ratio was lower in the tumor compared with the contralateral NABP (P < .01). The tumor lactate/pyruvate (LP) ratio was not different to NABP (P = .38). The LP and BP ratios in NABP were higher than those observed previously in normal volunteers (P < .05). Tumor lactate and bicarbonate signals were strongly correlated with the pyruvate signal (rho= 0.92, P < .001 and rho= 0.66, P < .001, respectively), and the LP ratio was weakly correlated with lactate dehydrogenase A (LDH-A) expression in biopsy samples (rho= 0.43, P = .04).
Conclusion
HP 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors compared with the surrounding NABP.
Sponsorship
Wellcome Trust (095962/Z/11/Z)
Cancer Research UK (CB4100)
Cancer Research UK (C14303/A17197)
Cancer Research Uk (None)
Embargo Lift Date
2025-05-26
Identifiers
This record's DOI: https://doi.org/10.17863/CAM.84933
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337518
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