Hyperpolarized [U-2H, U-13C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells

Abstract

Purpose A resonance at ∼181 ppm in the 13C spectra of tumors injected with hyperpolarized [U-2H, U-13C]glucose was assigned to 6-phosphogluconate (6PG), as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak assignments were investigated here using measurements of 6PG and 3PG 13C-labeling using liquid chromatography tandem mass spectrometry (LC-MS/MS) Methods Tumor-bearing mice were injected with 13C6 glucose and the 13C-labeled and total 6PG and 3PG concentrations measured. 13C MR spectra of glucose-6-phosphate dehydrogenase deficient (zwf1Δ) and wild-type yeast were acquired following addition of hyperpolarized [U-2H, U-13C]glucose and again 13C-labeled and total 6PG and 3PG were measured by LC-MS/MS Results Tumor 13C-6PG was more abundant than 13C-2PG/3PG and the resonance at ∼181 ppm matched more closely that of 6PG. 13C MR spectra of wild-type and zwf1Δ yeast cells showed a resonance at ∼181 ppm after labeling with hyperpolarized [U-2H, U-13C]glucose, however, there was no 6PG in zwf1Δ cells. In the wild-type cells 3PG was approximately four-fold more abundant than 6PG Conclusion The resonance at ∼181 ppm in 13C MR spectra following injection of hyperpolarized [U-2H, U-13C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells. Magn Reson Med 74:1543-1547, 2015.