Abstract
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Objectives Unique metabolism of choline (CHOL) in cancer cells has been used as the basis for molecular imaging with PET. In this study, the metabolism of CHOL was evaluated in a woodchuck HCC cell line WCH17 against the primary hepatocytes. The CHOL transporter (CHOT) was also characterized in WCH17 to determine the uptake mechanisms of CHOL in PET imaging of HCC.
Methods WCH17 cells and rat hepatocytes were pulsed with 14C-CHOL for 5 min and then chased in cold media to simulate the rapid circulation and clearance of 11C-CHOL. The cellular 14C metabolites were extracted and analyzed by HPLC. The uptake rate of CHOL in WCH17 was quantified for the properties of CHOT.
Results WCH17 cells showed higher 14C uptake than rat hepatocytes. 14C-Phosphocholine (PCho) was the major metabolite in WCH17. In contrast, the intracellular CHOL in primary hepatocytes was oxidized to betaine (partially released into media) and to a less degree, phosphorylated to PCho. With the physiological CHOL concentration, the facilitative transport is the major transport mechanism in WCH17 cells. CHOT in WCH17 is Na+ dependent and HC-3 sensitive. In contrast, CHOT in rat hepatocytes is Na+ independent, both with low affinity.
Conclusions Our data suggest that transport and phosphorylation of CHOL are responsible for the tracer accumulation during 11C-CHOL PET imaging of HCC. WCH17 cells incorporate 14C-CHOL preferentially into PCho. Conversion of 14C-PCho into phosphatidylcholine occurred slowly. Basal oxidation and phosphorylation activities in surrounding hepatic tissue contribute to the background seen in 11C-CHOL PET images.
Research Support NIH R01 CA095307
- © 2009 by Society of Nuclear Medicine