Reversed metabolic reprogramming as a measure of cancer treatment efficacy in rat C6 glioma model

Autor: Daniel M. Spielman, Keshav Datta, Lawrence Recht, Taichang Jang, Shie-Chau Liu, Milton Merchant, Ralph E. Hurd, Mette H. Lauritzen
Rok vydání: 2019
Předmět:
Male
Vascular Endothelial Growth Factor A
Magnetic Resonance Spectroscopy
Cancer Treatment
Biochemistry
Oxidative Phosphorylation
030218 nuclear medicine & medical imaging
Diagnostic Radiology
chemistry.chemical_compound
0302 clinical medicine
Antineoplastic Agents
Immunological
Drug Metabolism
Glucose Metabolism
Medicine and Health Sciences
Metabolites
Glycolysis
Neurological Tumors
Multidisciplinary
Brain Neoplasms
Radiology and Imaging
Magnetic resonance spectroscopic imaging
Brain
Glioma
Prognosis
Warburg effect
Magnetic Resonance Imaging
3. Good health
Survival Rate
Chemistry
Treatment Outcome
Oncology
Neurology
Physical Sciences
Medicine
Carbohydrate Metabolism
Research Article
medicine.medical_specialty
Imaging Techniques
Science
Bicarbonate
Oxidative phosphorylation
Research and Analysis Methods
03 medical and health sciences
In vivo
Diagnostic Medicine
Internal medicine
medicine
Animals
Pharmacokinetics
Lactic Acid
Rats
Wistar
Pharmacology
business.industry
Euthanasia
Chemical Compounds
Cancers and Neoplasms
Biology and Life Sciences
Metabolism
medicine.disease
Rats
Bicarbonates
Endocrinology
chemistry
business
030217 neurology & neurosurgery
Biomarkers
Neoplasm Transplantation
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 12, p e0225313 (2019)
ISSN: 1932-6203
Popis: BackgroundMetabolism in tumor shifts from oxidative phosphorylation to inefficient glycolysis resulting in overproduction of lactate (Warburg effect), and cancers may be effectively treated if this imbalance were corrected. The aim of this longitudinal study of glioblastoma in a rat model was to determine whether the ratio of lactate (surrogate marker for glycolysis) to bicarbonate (for oxidative phosphorylation), as measured via in vivo magnetic resonance imaging of hyperpolarized 13C-labeled pyruvate accurately predicts survival.MethodsC6 Glioma implanted male Wistar rats (N = 26) were treated with an anti-vascular endothelial growth factor antibody B20.4.1.1 in a preliminary study to assess the efficacy of the drug. In a subsequent longitudinal survival study, magnetic resonance spectroscopic imaging (MRSI) was used to estimate [1-13C]Lactate and [1-13C]Bicarbonate in tumor and contralateral normal appearing brain of glioma implanted rats (N = 13) after injection of hyperpolarized [1-13C]Pyruvate at baseline and 48 hours post-treatment with B20.4.1.1.ResultsA survival of ~25% of B20.4.1.1 treated rats was noted in the preliminary study. In the longitudinal imaging experiment, changes in 13C Lactate, 13C Bicarbonate and tumor size measured at baseline and 48 hours post-treatment did not correlate with survival. 13C Lactate to 13C Bicarbonate ratio increased in all the 6 animals that succumbed to the tumor whereas the ratio decreased in 6 of the 7 animals that survived past the 70-day observation period.Conclusions13C Lactate to 13C Bicarbonate ratio (Lac/Bic) at 48 hours post-treatment is highly predictive of survival (p = 0.003). These results suggest a potential role for the 13C Lac/Bic ratio serving as a valuable measure of tumor metabolism and predicting therapeutic response.
Databáze: OpenAIRE
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