Imaging of glucose metabolism by 13C-MRI distinguishes pancreatic cancer subtypes in mice

  1. Shun Kishimoto
  2. Jeffrey R Brender  Is a corresponding author
  3. Daniel R Crooks
  4. Shingo Matsumoto
  5. Tomohiro Seki
  6. Nobu Oshima
  7. Hellmut Merkle
  8. Penghui Lin
  9. Galen Reed
  10. Albert P Chen
  11. Jan Henrik Ardenkjaer-Larsen
  12. Jeeva Munasinghe
  13. Keita Saito
  14. Kazutoshi Yamamoto
  15. Peter L Choyke
  16. James Mitchell
  17. Andrew N Lane
  18. Teresa WM Fan
  19. W Marston Linehan
  20. Murali C Krishna  Is a corresponding author
  1. NCI, NIH, United States
  2. Urologic Oncology Branch, Center for Cancer Research, NCI, NIH, United States
  3. Hokkaido University, Japan
  4. JST, PREST, Japan
  5. NIH, United States
  6. University of Kentucky, United States
  7. GE HealthCare, United States
  8. Technical University of Denmark, Denmark
5 figures and 1 additional file

Figures

Figure 1 with 3 supplements
Distinct anatomical microstructure differences exist between Hs 766T and MIA Paca-2 xenografts while CE-MS shows only subtle metabolic differences.

(A and C) T2 weighted anatomical RARE images of (A) Hs 766T and (C) MIA Paca-2 PDAC xenografts implanted on the left leg. Focal necrosis is evident in the Hs 766T tumor, but not in the MIA Paca-2 …

https://doi.org/10.7554/eLife.46312.002
Figure 1—figure supplement 1
Protein expression levels from immunoblotting of tumor extracts of key proteins associated with metabolism.

Su86.86 forms a distinct subtype with statistically significant differences of the glucose transporter one and the angiogenic factor CD31. Error bars represent standard deviation (n = 4).

https://doi.org/10.7554/eLife.46312.003
Figure 1—figure supplement 2
Metabolite differences between normal tissue and the MIA Paca-2 PDAC leg xenografts as analyzed by CE/MS.

White boxes indicate metabolites not detected. Gray boxes indicate a statistically insignificant difference between cell lines (two-sided t-test, corrected for multiple comparisons by the two-stage …

https://doi.org/10.7554/eLife.46312.004
Figure 1—figure supplement 3
Metabolic differences within glycolysis between normal tissue and MIA Paca-2 and Hs 766T PDAC leg xenografts in terms of absolute concentrations (nmol/g tumor wet weight).

Differences between normal tissue and cancerous can be seen throughout. Hs 766T and MIA Paca-2 diverge after the pentose phosphate shunt at glyceraldehyde-3-phosphate.

https://doi.org/10.7554/eLife.46312.005
Pyruvate metabolism is similar in Hs 766T and MIA Paca-2 Xenografts.

(A and B) Representative signal after injecting 300 µL of 98 mM hyperpolarized [1-13C] pyruvate into the tail vein of a mouse of a nude mouse with either a (A) Hs 766T or (B) MiaPaCa2 leg xenograft. …

https://doi.org/10.7554/eLife.46312.006
Figure 3 with 1 supplement
Glucose metabolism differentiates Hs 766T and MiaPaca2 xenografts.

(A) Representative signal before and 1 hr after injecting 50 mg of [U-13C] glucose into the tail vein of a mouse of a nude mouse with a MIA Paca-2 leg xenograft. The largest signal at 32 ppm is due …

https://doi.org/10.7554/eLife.46312.007
Figure 3—figure supplement 1
Ex vivo NMR analysis of Hs766T and MIA Paca-2 xenografts.

(A) Representative multiplicity edited HSQC from the polar fraction of a Hs 766T xenograft. The sign of the peak is reflective of the proton connectivity of the carbon: positive peaks (red) arise …

https://doi.org/10.7554/eLife.46312.008
CSI imaging of a Hs 766T mouse leg xenograft after a 50 mg [U-13C] glucose injection in a volume of 300 microliters of PBS.

An 8 × 8 image of the tumor bearing mouse leg was acquired by chemical shift imaging every 48 s for 60 min. The final image was zero-filled to 16 × 16. Each is voxel 0.15 cm x 0.15 cm x 1.6 cm in …

https://doi.org/10.7554/eLife.46312.009
Contour maps created from time averages of the peak maxia of the glucose and lactate signals for three representative MIA Paca-2 (left) and Hs 766T (right) tumors.
https://doi.org/10.7554/eLife.46312.010

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