title: Imaging lipid synthesis in hepatocellular carcinoma with [methyl-11c]choline: correlation with in vivo metabolic studies.
abstract: PET with [methyl-(11)C]-choline (11C-choline) can be useful for detecting well-differentiated hepatocellular carcinoma (HCC) that is not 18F-FDG-avid. This study was designed to examine the relationship between choline metabolism and choline tracer uptake in HCC for PET with 11C-choline.
  
  
  METHODS
  Dynamic PET scans of 11C-choline were acquired using the woodchuck models of HCC. After imaging, [methyl-(14)C]-choline was injected, and metabolites from both HCC tissue samples and the surrounding hepatic tissues were extracted and analyzed by radio-high-performance liquid chromatography. The enzymatic activities of choline kinase and choline-phosphate cytidylyltransferase were assayed for correlation with the imaging and metabolism data.
  
  
  RESULTS
  PET with 11C-choline showed an HCC detection rate of 9 of 10. The tumor-to-liver ratio for the 9 detected HCCs was 1.89±0.55. Hematoxylin-eosin staining confirmed that all spots with high tracer uptake were well-differentiated HCCs. Variation of radioactivity distribution within HCCs indicated a heterogeneous uptake of choline. The activities of both choline kinase and choline-phosphate cytidylyltransferase were found to be significantly higher in HCC than in the surrounding hepatic tissues. The major metabolites of 11C-choline were phosphocholine in HCC and betaine and choline in the surrounding hepatic tissues at 12 min after injection; in HCC, phosphocholine rapidly converted to phosphatidylcholine at 30 min after injection.
  
  
  CONCLUSIONS
  HCCs display enhanced uptake of radiolabeled choline despite a moderate degree of physiologic uptake in the surrounding hepatic tissues. Initially, increased radiolabeled choline uptake in HCCs is associated with the transport and phosphorylation of choline; as time passes, the increased uptake of radiolabeled choline reflects increased phosphatidylcholine synthesis derived from radiolabeled cytidine 5'-diphosphocholine (CDP-choline) in HCCs. In contrast, the surrounding hepatic tissues exhibit extensive oxidation of radiolabeled choline via the phosphatidylethanolamine methylation pathway, a major contributor to the observed physiologic uptake.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, and Department of Radiology, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kuang
authors.forename: Nicolas
authors.initials: N
authors.lastname: Salem
authors.forename: Haibin
authors.initials: H
authors.lastname: Tian
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kolthammer
authors.forename: David J
authors.initials: DJ
authors.lastname: Corn
authors.forename: Chunying
authors.initials: C
authors.lastname: Wu
authors.forename: Fangjing
authors.initials: F
authors.lastname: Wang
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Lee
mesh_terms: D000818:Animals; D001622:Betaine / Q000378:metabolism; D002250:Carbon Radioisotopes; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D002797:Choline Kinase / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D008055:Lipids / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000378:metabolism*; D008392:Marmota; D010713:Phosphatidylcholines / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D002250:Carbon Radioisotopes; D008055:Lipids; D010713:Phosphatidylcholines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D001622:Betaine; D002797:Choline Kinase; D019916:Choline-Phosphate Cytidylyltransferase; D002794:Choline