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

Author:

Kishimoto Shun1ORCID,Brender Jeffrey R1ORCID,Crooks Daniel R2,Matsumoto Shingo34,Seki Tomohiro1,Oshima Nobu1,Merkle Hellmut5,Lin Penghui6,Reed Galen7,Chen Albert P7,Ardenkjaer-Larsen Jan Henrik78,Munasinghe Jeeva5,Saito Keita1,Yamamoto Kazutoshi1,Choyke Peter L9,Mitchell James1,Lane Andrew N610,Fan Teresa WM610,Linehan W Marston2,Krishna Murali C1ORCID

Affiliation:

1. Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, United States

2. Urologic Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, United States

3. Graduate School of Information Science and Technology, Division of Bioengineering and Bioinformatics, Hokkaido University, Sapporo, Japan

4. JST, PREST, Saitama, Japan

5. NINDS, NIH, Bethesda, United States

6. Center for Environmental and Systems Biochemistry, University of Kentucky, Lexington, United States

7. GE HealthCare, Chicago, United States

8. Department of Electrical Engineering, Technical University of Denmark, Kongens Lyngby, Denmark

9. Molecular Imaging Program, Center for Cancer Research, NCI, NIH, Bethesda, United States

10. Markey Cancer Center, University of Kentucky, Lexington, United States

Abstract

Metabolic differences among and within tumors can be an important determinant in cancer treatment outcome. However, methods for determining these differences non-invasively in vivo is lacking. Using pancreatic ductal adenocarcinoma as a model, we demonstrate that tumor xenografts with a similar genetic background can be distinguished by their differing rates of the metabolism of 13C labeled glucose tracers, which can be imaged without hyperpolarization by using newly developed techniques for noise suppression. Using this method, cancer subtypes that appeared to have similar metabolic profiles based on steady state metabolic measurement can be distinguished from each other. The metabolic maps from 13C-glucose imaging localized lactate production and overall glucose metabolism to different regions of some tumors. Such tumor heterogeneity would not be not detectable in FDG-PET.

Funder

National Cancer Institute

Shared Resource(s) of the University of Kentucky Markey Cancer Center

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference82 articles.

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4. Hexokinase 2 promotes tumor growth and metastasis by regulating lactate production in pancreatic Cancer;Anderson;Oncotarget,2017

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