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[11C]acetate PET Imaging is not Always Associated with Increased Lipogenesis in Hepatocellular Carcinoma in Mice

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Abstract

Purpose

Altered metabolism, including increased glycolysis and de novo lipogenesis, is one of the hallmarks of cancer. Radiolabeled nutrients, including glucose and acetate, are extensively used for the detection of various tumors, including hepatocellular carcinomas (HCCs). High signal of [11C]acetate positron emission tomography (PET) in tumors is often considered to be associated with increased expression of fatty acid synthase (FASN) and increased de novo lipogenesis in tumor tissues. Defining a subset of tumors with increased [11C]acetate PET signal and thus increased lipogenesis was suggested to help select a group of patients, who may benefit from lipogenesis-targeting therapies.

Procedures

To investigate whether [11C]acetate PET imaging is truly associated with increased de novo lipogenesis along with hepatocarcinogenesis, we performed [11C]acetate PET imaging in wild-type mice as well as two mouse HCC models, induced by myrAKT/RasV12 (AKT/Ras) and PIK3CA1047R/c-Met (PI3K/Met) oncogene combinations. In addition, we analyzed FASN expression and de novo lipogenesis rate in these mouse liver tissues.

Results

We found that while HCCs induced by AKT/Ras co-expression showed high levels of [11C]acetate PET signal compared to normal liver, HCCs induced by PI3K/Met overexpression did not. Intriguingly, elevated FASN expression and increased de novo lipogenesis rate were observed in both AKT/Ras and PI3K/Met HCCs.

Conclusion

Altogether, our study suggests that [11C]acetate PET imaging can be a useful tool for imaging of a subset of HCCs. However, at molecular level, the increased [11C]acetate PET imaging is not always associated with increased FASN expression or de novo lipogenesis.

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Acknowledgments

We would like to thank Mariia Yuneva for her thoughtful comments for the manuscript. We also thank Stephanie T. Murphy for her immense help on animal imaging. This work was supported in part by the University of California, San Francisco (UCSF) Radiology Seed Grant, UCSF Liver Center Pilot/Feasibility Grant (P30DK026743), National Institutes of Health/National Cancer Institute (NIH/NCI), and UCSF Helen Diller Family Comprehensive Cancer Center (P30CA082103) to Youngho Seo; NIH/NCI grant (R01CA136606) to Xin Chen; NIH (U24DK76174) to Case Western Reserve University Mouse Metabolic Phenotyping Center (MMPC); and the National Natural Science Foundation of China (Grant No. 81201553) to Lei Li.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Lei Li

  2. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, 94143-0912, USA

    Lei Li, Li Che, Chunmei Wang, Xiaolei Li & Xin Chen

  3. Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA

    Joseph E. Blecha, Henry F. VanBrocklin & Youngho Seo

  4. Institute of Pathology, University of Greifswald, Greifswald, Germany

    Diego F. Calvisi

  5. Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA

    Michelle Puchowicz

  6. Department of Radiation Oncology, University of California, San Francisco, CA, USA

    Youngho Seo

  7. UCSF-UC Berkeley Joint Graduate Group in Bioengineering, University of California, San Francisco, CA, USA

    Youngho Seo

  8. Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Youngho Seo

  9. UCSF Physics Research Laboratory, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143-0946, USA

    Youngho Seo

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  1. Lei Li
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  2. Li Che
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Correspondence to Xin Chen or Youngho Seo.

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Li, L., Che, L., Wang, C. et al. [11C]acetate PET Imaging is not Always Associated with Increased Lipogenesis in Hepatocellular Carcinoma in Mice. Mol Imaging Biol 18, 360–367 (2016). https://doi.org/10.1007/s11307-015-0915-8

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