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

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.