title: [(11)C]acetate PET Imaging is not Always Associated with Increased Lipogenesis in Hepatocellular Carcinoma in Mice.
abstract: 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 [(11)C]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 [(11)C]acetate PET signal and thus increased lipogenesis was suggested to help select a group of patients, who may benefit from lipogenesis-targeting therapies.
  
  
  
  To investigate whether [(11)C]acetate PET imaging is truly associated with increased de novo lipogenesis along with hepatocarcinogenesis, we performed [(11)C]acetate PET imaging in wild-type mice as well as two mouse HCC models, induced by myrAKT/Ras(V12) (AKT/Ras) and PIK3CA(1047R)/c-Met (PI3K/Met) oncogene combinations. In addition, we analyzed FASN expression and de novo lipogenesis rate in these mouse liver tissues.
  
  
  
  We found that while HCCs induced by AKT/Ras co-expression showed high levels of [(11)C]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.
  
  
  
  Altogether, our study suggests that [(11)C]acetate PET imaging can be a useful tool for imaging of a subset of HCCs. However, at molecular level, the increased [(11)C]acetate PET imaging is not always associated with increased FASN expression or de novo lipogenesis.
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, 94143-0912, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, 94143-0912, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Che
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, 94143-0912, USA.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Blecha
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, 94143-0912, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors.forename: Henry F
authors.initials: HF
authors.lastname: VanBrocklin
authors.affiliation: Institute of Pathology, University of Greifswald, Greifswald, Germany.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Calvisi
authors.affiliation: Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Puchowicz
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, 94143-0912, USA. xin.chen@ucsf.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA. youngho.seo@ucsf.edu.|Department of Radiation Oncology, University of California, San Francisco, CA, USA. youngho.seo@ucsf.edu.|UCSF-UC Berkeley Joint Graduate Group in Bioengineering, University of California, San Francisco, CA, USA. youngho.seo@ucsf.edu.|Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. youngho.seo@ucsf.edu.|UCSF Physics Research Laboratory, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143-0946, USA. youngho.seo@ucsf.edu.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Seo
mesh_terms: D000085:Acetates / Q000737:chemistry*; D000818:Animals; D002250:Carbon Radioisotopes; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism; D050155:Lipogenesis; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000085:Acetates; D002250:Carbon Radioisotopes; D014280:Triglycerides; D002784:Cholesterol; D019869:Phosphatidylinositol 3-Kinases; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; D018631:ras Proteins
keywords: De novo lipogenesis; Fatty acid synthase expression; Hepatocellular carcinoma; PET; [11C]acetate