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

Abstract

Purpose: To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods: In this prospective study, seven treatment-naive patients (age [mean 6 SD], 60 years 6 11; five men) with GBM were imaged at 3 T by using a dual-tuned13C–hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was ac-quired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchy-ma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman r correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemi-cal 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 (r = 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 (r = 0.43, P = .04). Conclusion: Hyperpolarized 13C 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.