Dual inhibition of oxidative phosphorylation and glycolysis exerts a synergistic antitumor effect on colorectal and gastric cancer by creating energy depletion and preventing metabolic switch
Fig 4
Monitoring dynamic metabolic changes in tumor xenografts using 13C-MRSI with hyperpolarized 1-13C pyruvate.
(A)Schematic representation of HP 1-13C pyruvate MR study: 13C MR was performed using mice bearing HCT116 and MKN45 xenografts. Each mouse was imaged 30 minutes after NCI-006 administration and/or 3 h after IACS-010759 administration. (B)13C chemical shift of 1-13C lactate, 1-13C hydrate pyruvate, and 1-13C pyruvate. (C)Representative 13C-MR signal intensity curves of 1-13C pyruvate and 1-13C lactate detected in HCT116 and MKN45 xenografts after hyperpolarized 1-13C pyruvate injection. (D)The 1-13C-Lactate/Pyruvate ratio in ex vivo experiments. The ex vivo data were obtained from tumor tissue samples extracted and homogenized after each treatment. The 1-13C Lac/Pyr ratio was calculated from the Area Under Curve (AUC) using time-intensity data. (E)The 1-13C-Lactate/Pyruvate ratio in vivo experiments. HP-MRSI, hyperpolarized 13C-magnetic resonance spectroscopic imaging.