Metabolic Imaging of the Human Brain with Hyperpolarized C Pyruvate Demonstrates C Lactate Production in Brain Tumor Patients

Overview

Journal Cancer Res

Specialty Oncology

Date 2018 May 18

PMID 29769199

Citations 130

Authors

Vesselin Z Miloushev

Kristin L Granlund

Rostislav Boltyanskiy

Serge K Lyashchenko

Lisa M DeAngelis

Ingo K Mellinghoff

Cameron W Brennan

Vivian Tabar

T Jonathan Yang

Andrei I Holodny

Ramon E Sosa

YanWei W Guo

Albert P Chen

James Tropp

Fraser Robb

Kayvan R Keshari

Affiliations

Soon will be listed here.

Abstract

Hyperpolarized (HP) MRI using [1-13C] pyruvate is a novel method that can characterize energy metabolism in the human brain and brain tumors. Here, we present the first dynamically acquired human brain HP 13C metabolic spectra and spatial metabolite maps in cases of both untreated and recurrent tumors. production of HP lactate from HP pyruvate by tumors was indicative of altered cancer metabolism, whereas production of HP lactate in the entire brain was likely due to baseline metabolism. We correlated our results with standard clinical brain MRI, MRI DCE perfusion, and in one case FDG PET/CT. Our results suggest that HP 13C pyruvate-to-lactate conversion may be a viable metabolic biomarker for assessing tumor response. Hyperpolarized pyruvate MRI enables metabolic imaging in the brain and can be a quantitative biomarker for active tumors. http://cancerres.aacrjournals.org/content/canres/78/14/3755/F1.large.jpg .

Citing Articles

[Research Progress in Applying Hyperpolarized C Labeling Technology in Neurological Metabolic Diagnostics].

He C, He H, Yang X, Xing H, Lyu S, Wu M Sichuan Da Xue Xue Bao Yi Xue Ban. 2025; 55(6):1343-1349.

PMID: 39990827 PMC: 11839364. DOI: 10.12182/20241160101.

Task activation results in regional C-lactate signal increase in the human brain.

Uthayakumar B, Cappelletto N, Bragagnolo N, Chen A, Ma N, Perks W J Cereb Blood Flow Metab. 2025; :271678X251314683.

PMID: 39862181 PMC: 11765303. DOI: 10.1177/0271678X251314683.

Simultaneous noninvasive quantification of redox and downstream glycolytic fluxes reveals compartmentalized brain metabolism.

Patel S, Porcari P, Coffee E, Kim N, Berishaj M, Peyear T Sci Adv. 2024; 10(51):eadr2058.

PMID: 39705365 PMC: 11661454. DOI: 10.1126/sciadv.adr2058.

Hyperpolarized Nano-NMR Platform for Quantification of Mass Limited Samples.

Pigliapochi R, Peyear T, Ruan T, Keshari K Anal Chem. 2024; .

PMID: 39034921 PMC: 11751133. DOI: 10.1021/acs.analchem.4c02378.

Imaging brain glucose metabolism in vivo reveals propionate as a major anaplerotic substrate in pyruvate dehydrogenase deficiency.

Marin-Valencia I, Kocabas A, Rodriguez-Navas C, Miloushev V, Gonzalez-Rodriguez M, Lees H Cell Metab. 2024; 36(6):1394-1410.e12.

PMID: 38838644 PMC: 11187753. DOI: 10.1016/j.cmet.2024.05.002.

References

Warburg O . On the origin of cancer cells. Science. 1956; 123(3191):309-14. DOI: 10.1126/science.123.3191.309. View

Wen P, Chang S, van den Bent M, Vogelbaum M, Macdonald D, Lee E . Response Assessment in Neuro-Oncology Clinical Trials. J Clin Oncol. 2017; 35(21):2439-2449. PMC: 5516482. DOI: 10.1200/JCO.2017.72.7511. View

Chaumeil M, Ozawa T, Park I, Scott K, James C, Nelson S . Hyperpolarized 13C MR spectroscopic imaging can be used to monitor Everolimus treatment in vivo in an orthotopic rodent model of glioblastoma. Neuroimage. 2011; 59(1):193-201. PMC: 3196046. DOI: 10.1016/j.neuroimage.2011.07.034. View

Park J, Josan S, Jang T, Merchant M, Yen Y, Hurd R . Metabolite kinetics in C6 rat glioma model using magnetic resonance spectroscopic imaging of hyperpolarized [1-(13)C]pyruvate. Magn Reson Med. 2012; 68(6):1886-93. PMC: 3376665. DOI: 10.1002/mrm.24181. View

Bulik M, Jancalek R, Vanicek J, Skoch A, Mechl M . Potential of MR spectroscopy for assessment of glioma grading. Clin Neurol Neurosurg. 2012; 115(2):146-53. DOI: 10.1016/j.clineuro.2012.11.002. View

Park I, Bok R, Ozawa T, Phillips J, James C, Vigneron D . Detection of early response to temozolomide treatment in brain tumors using hyperpolarized 13C MR metabolic imaging. J Magn Reson Imaging. 2011; 33(6):1284-90. PMC: 4983457. DOI: 10.1002/jmri.22563. View

Gonzalez S, Nguyen N, Rise F, Hassel B . Brain metabolism of exogenous pyruvate. J Neurochem. 2005; 95(1):284-93. DOI: 10.1111/j.1471-4159.2005.03365.x. View

Golman K, Ardenkjaer-Larsen J, Petersson J, Mansson S, Leunbach I . Molecular imaging with endogenous substances. Proc Natl Acad Sci U S A. 2003; 100(18):10435-9. PMC: 193579. DOI: 10.1073/pnas.1733836100. View

Keshari K, Wilson D . Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization. Chem Soc Rev. 2013; 43(5):1627-59. PMC: 4086923. DOI: 10.1039/c3cs60124b. View

10.

Park I, Larson P, Tropp J, Carvajal L, Reed G, Bok R . Dynamic hyperpolarized carbon-13 MR metabolic imaging of nonhuman primate brain. Magn Reson Med. 2013; 71(1):19-25. PMC: 4041734. DOI: 10.1002/mrm.25003. View

11.

Ward P, Thompson C . Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell. 2012; 21(3):297-308. PMC: 3311998. DOI: 10.1016/j.ccr.2012.02.014. View

12.

Law M, Yang S, Wang H, Babb J, Johnson G, Cha S . Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol. 2003; 24(10):1989-98. PMC: 8148904. View

13.

Huang R, Neagu M, Reardon D, Wen P . Pitfalls in the neuroimaging of glioblastoma in the era of antiangiogenic and immuno/targeted therapy - detecting illusive disease, defining response. Front Neurol. 2015; 6:33. PMC: 4337341. DOI: 10.3389/fneur.2015.00033. View

14.

Petrella J, Provenzale J . MR perfusion imaging of the brain: techniques and applications. AJR Am J Roentgenol. 2000; 175(1):207-19. DOI: 10.2214/ajr.175.1.1750207. View

15.

Maher E, Marin-Valencia I, Bachoo R, Mashimo T, Raisanen J, Hatanpaa K . Metabolism of [U-13 C]glucose in human brain tumors in vivo. NMR Biomed. 2012; 25(11):1234-44. PMC: 3406255. DOI: 10.1002/nbm.2794. View

16.

Ardenkjaer-Larsen J, Fridlund B, Gram A, Hansson G, Hansson L, Lerche M . Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A. 2003; 100(18):10158-63. PMC: 193532. DOI: 10.1073/pnas.1733835100. View

17.

Hu S, Balakrishnan A, Bok R, Anderton B, Larson P, Nelson S . 13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression. Cell Metab. 2011; 14(1):131-42. PMC: 3858338. DOI: 10.1016/j.cmet.2011.04.012. View

18.

Nelson S, Kurhanewicz J, Vigneron D, Larson P, Harzstark A, Ferrone M . Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate. Sci Transl Med. 2013; 5(198):198ra108. PMC: 4201045. DOI: 10.1126/scitranslmed.3006070. View

19.

Venneti S, Dunphy M, Zhang H, Pitter K, Zanzonico P, Campos C . Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Sci Transl Med. 2015; 7(274):274ra17. PMC: 4431550. DOI: 10.1126/scitranslmed.aaa1009. View