title: Hepatic gluconeogenesis influences (13)C enrichment in lactate in human brain tumors during metabolism of [1,2-(13)C]acetate.
abstract: (13)C-enriched compounds are readily metabolized in human malignancies. Fragments of the tumor, acquired by biopsy or surgical resection, may be acid-extracted and (13)C NMR spectroscopy of metabolites such as glutamate, glutamine, 2-hydroxyglutarate, lactate and others provide a rich source of information about tumor metabolism in situ. Recently we observed (13)C-(13)C spin-spin coupling in (13)C NMR spectra of lactate in brain tumors removed from patients who were infused with [1,2-(13)C]acetate prior to the surgery. We found, in four patients, that infusion of (13)C-enriched acetate was associated with synthesis of (13)C-enriched glucose, detectable in plasma. (13)C labeled glucose derived from [1,2-(13)C]acetate metabolism in the liver and the brain pyruvate recycling in the tumor together lead to the production of the (13)C labeled lactate pool in the brain tumor. Their combined contribution to acetate metabolism in the brain tumors was less than 4.0%, significantly lower than the direct oxidation of acetate in the citric acid cycle in tumors.
authors.affiliation: Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: kpichumani@houstonmethodist.org.
authors.forename: Kumar
authors.initials: K
authors.lastname: Pichumani
authors.affiliation: Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mashimo
authors.affiliation: Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Vamsidhara
authors.initials: V
authors.lastname: Vemireddy
authors.affiliation: Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kovacs
authors.affiliation: Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: James
authors.initials: J
authors.lastname: Ratnakar
authors.affiliation: Department of Neurological Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Mickey
authors.affiliation: Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Radiology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Veterans Affairs North Texas HealthCare System, Lancaster, TX 75216, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
authors.affiliation: Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX 75390, USA; McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX 75390, USA; Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.affiliation: Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bachoo
authors.affiliation: Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Maher
mesh_terms: D000085:Acetates / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002247:Carbon Isotopes / Q000378:metabolism*; D005943:Gluconeogenesis / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods
chemical_list: D000085:Acetates; D002247:Carbon Isotopes; D019344:Lactic Acid
keywords: Brain metastases; Glioblastoma; Isotopomers; Metabolism; Pyruvate recycling; [1,2-(13)C]acetate