Fig 3. The combination therapy of CPI-613 and CHC (solvent: DMSO) did not lead to a significant reduction of tumor growth in vivo.

(A) To evaluate the efficacy of the combinatorial therapy in the orthotopic pancreatic cancer model CPI-613 (25 mg/kg) was injected once a week and CHC (15 mg/kg) was applied on a daily basis from day 4 until the end of the experiment day 37. Both therapeutics were dissolved in DMSO (CPI: 100% DMSO, CHC: 50% DMSO/ 50% PBS), the sham animals were treated with the respective vehicle of the combinatorial treatment. (B-C) PET-CT imaging with the tracer ¹⁸F-FDG was performed to quantify changes in the glucose metabolism of tumor tissue. (D) The uptake of ¹⁸F-FDG in the tumor tissue was evaluated by metabolic tumor volume (MTV, tumor volume [mm³] with the criteria 30% of the hottest voxel of injected dose/g bodyweight) on day 32 after tumor cell implantation on a subset of sham and CPI + CHC tumors. (E) Tumor weight was measured at the end of the experiment in the indicated treatment groups. (F) The body weight of mice was measured at the indicated days during the treatment period and the body weight change was calculated from the weight assessed at the beginning of each experiment. Biological replicates: D: Sham n = 3, CPI + CHC n = 2. E-F: Sham n = 9, CPI n = 4, CPI + CHC n = 10, CHC n = 3.