Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-C-13]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study

Purpose: To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (C-13) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-C-13]pyruvate and tumor lactate and bicarbonate. Materials and Methods: In this prospective study, seven treatment-naive patients (age [mean +/- SD], 60 years +/- 11; five men) with GBM were imaged at 3 T by using a dual-tuned C-13-hydrogen 1 head coil. Hyperpolarized [1-C-13]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman rho correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results: The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P<.01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P=.38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P<.05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (rho = 0.92, P<.001, and r = 0.66, P<.001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (rho = 0.43, P = .04). Conclusion: Hyperpolarized C-13 MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Published under a CC BY 4.0 license.