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Hyperpolarized [U‐ 2 H, U‐ 13 C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells
Author(s) -
Timm Kerstin N.,
Hartl Johannes,
Keller Markus A.,
Hu DeEn,
Kettunen Mikko I.,
Rodrigues Tiago B.,
Ralser Markus,
Brindle Kevin M.
Publication year - 2015
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.25561
Subject(s) - chemistry , yeast , glycolysis , pentose phosphate pathway , radiochemistry , nuclear magnetic resonance , biochemistry , metabolism , physics
Purpose A resonance at ∼181 ppm in the 13 C spectra of tumors injected with hyperpolarized [U‐ 2 H, U‐ 13 C]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 13 C‐labeling using liquid chromatography tandem mass spectrometry (LC‐MS/MS) Methods Tumor‐bearing mice were injected with 13 C 6 glucose and the 13 C‐labeled and total 6PG and 3PG concentrations measured. 13 C MR spectra of glucose‐6‐phosphate dehydrogenase deficient ( zwf1 Δ) and wild‐type yeast were acquired following addition of hyperpolarized [U‐ 2 H, U‐ 13 C]glucose and again 13 C‐labeled and total 6PG and 3PG were measured by LC‐MS/MS Results Tumor 13 C‐6PG was more abundant than 13 C‐2PG/3PG and the resonance at ∼181 ppm matched more closely that of 6PG. 13 C MR spectra of wild‐type and zwf1 Δ yeast cells showed a resonance at ∼181 ppm after labeling with hyperpolarized [U‐ 2 H, U‐ 13 C]glucose, however, there was no 6PG in zwf1 Δ cells. In the wild‐type cells 3PG was approximately four‐fold more abundant than 6PG Conclusion The resonance at ∼181 ppm in 13 C MR spectra following injection of hyperpolarized [U‐ 2 H, U‐ 13 C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells. Magn Reson Med 74:1543–1547, 2015. © 2014 Wiley Periodicals, Inc.