title: 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.
abstract: 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) C6 glucose and the (13) C-labeled and total 6PG and 3PG concentrations measured. (13) C MR spectra of glucose-6-phosphate dehydrogenase deficient (zwf1Δ) 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 zwf1Δ 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 zwf1Δ 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.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kerstin N
authors.initials: KN
authors.lastname: Timm
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hartl
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Keller
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: De-En
authors.initials: DE
authors.lastname: Hu
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Kettunen
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Tiago B
authors.initials: TB
authors.lastname: Rodrigues
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom.
authors.forename: Markus
authors.initials: M
authors.lastname: Ralser
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D006019:Glycolysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010427:Pentose Phosphate Pathway; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012680:Sensitivity and Specificity; D014501:Uranium / Q000493:pharmacokinetics*
chemical_list: D019275:Radiopharmaceuticals; D014501:Uranium; D005947:Glucose
keywords: glucose; hyperpolarized 13C; pentose phosphate pathway