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Metabolism of Radiolabeled Methionine in Hepatocellular Carcinoma.
MedLine Citation:
PMID:  23921714     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: Radiolabeled methionine (Met) promises to be useful in the positron emission tomography (PET) imaging of hepatocellular carcinoma (HCC). However, its metabolic routes in HCC have not yet been fully understood. In this study, the metabolic pathway(s) of radiolabeled Met in HCC were investigated.
PROCEDURES: To simulate the rapid blood clearance of radiolabeled Met, pulse-chase experiments were conducted. L-[methyl-(3)H]-Met or L-[1-(14)C]-Met was pulsed over control or cycloheximide-treated WCH17 cells and rat hepatocytes for 5 min and chased with cold media. The water-soluble, lipid-soluble, DNA, RNA, and protein phases were subsequently extracted and measured from the acid-precipitable and acid-soluble fractions of whole cells. The radioactive metabolites Met, S-adenosylmethionine (SAM), S-adenosylhomocysteine, Met sulfoxide, and Met sulfone were further separated by radio thin layer chromatography.
RESULTS: (1) The uptake of L-[methyl-(3)H]-Met in both cell types was higher than that of L-[1-(14)C]-Met. In rat hepatocytes, the uptake of L-[methyl-(3)H]-Met was significantly higher than that of L-[1-(14)C]-Met, which may contribute to its physiologic accumulation in surrounding hepatic tissues seen in PET imaging of HCC using L-[methyl-(11)C]-Met. Compared to rat hepatocytes, WCH17 cells had significantly higher uptake of both radiotracers. (2) For L-[methyl-(3)H]-Met, the major intracellular uptake was found mostly in the protein phase and, to a lesser degree, in the phosphatidylethanolamine (PE) methylation pathway, which is fairly stabilized within the 55-min chase period (the main metabolites were SAM, Met, Met sulfoxide, and Met sulfone). In contrast, the uptake of Met in rat hepatocytes mainly points to phosphatidylcholine (PC) synthesis through the PE methylation pathway (the main metabolite was PC). (3) Both cell types incorporated L-[1-(14)C]-Met predominantly into protein synthesis. (4) Finally, when the protein synthesis pathway was inhibited, the incorporation of SAM derived from L-[methyl-(3)H]-Met to lipid class (PC was the main metabolite) occurred at a reduced rate in WCH17 cells, suggesting that the route may be impaired in HCC.
CONCLUSIONS: This study demonstrated that different metabolic pathways of radiolabeled Met exist between HCC and surrounding hepatic tissue and contribute to the patterns of increased uptake of radiolabeled Met in HCC.
Authors:
Yu Kuang; Fangjing Wang; David J Corn; Haibin Tian; Zhenghong Lee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-8-7
Journal Detail:
Title:  Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging     Volume:  -     ISSN:  1860-2002     ISO Abbreviation:  Mol Imaging Biol     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-8-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101125610     Medline TA:  Mol Imaging Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Nuclear Medicine Division, Department of Radiology, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.
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