@misc{oai:repo.qst.go.jp:00071223,
 author = {Yoshii, Yukie and Furukawa, Takako and Yoshii, Hiroshi and Fujibayashi, Yasuhisa and 古川 高子 and 藤林 康久},
 month = {Sep},
 note = {Our previous study showed that acetate fixation into lipids is elevated in tumor cells: this characteristic underlies 11C-acetate PET of tumors. The pathway is considered to be driven by acetyl-CoA synthetase (Acss) converting acetate to acetyl-CoA. On the other hand, we found that tumor cells can also utilize a reverse reaction of Acss for ATP synthesis through acetate production, which resembles known pathway in ancient anaerobic organisms. These facts collectively point out that Acss manages both anabolism and catabolism of acetate coordinately in tumor cells.
Additionally, we found that expression of Acss was increased significantly under hypoxia, which indicates that total activity of acetate metabolism is up-regulated in hypoxic tumor cells. In this study, to confirm the above supposition and propose acetate PET as a new tumor metabolic imaging, we examined the characteristics of tumor acetate uptake under hypoxia.
We performed 14C-acetate uptake study using cultured mouse tumor cells in 24-well plates with fibroblast cells as control. Cells were incubated under normoxia for 24 h, then a part of them were treated by 2 h hypoxia. After preincubation, medium containing 1mu Ci 14C-acetate was added to each well and the cells were further incubated for 1 h under the same condition. After cell lyses, radioactivity was measured by a liquid scintillation counter. To verify the role of Acss, we also examined 14C-acetate uptake in Acss-knockdown tumor cells.
Our data demonstrated that 14C-acetate uptake was higher under hypoxia than normoxia in tumor cells, but not in normal cells, and that knock down of Acss decreased 14C-acetate uptake in tumor cells. Based on these results, we concluded that tumor acetate metabolism mediated by Acss was up-regulated under hypoxia, which caused the increase of 14C-acetate uptake. These findings suggest a possibility that 11C-acetate PET is visualizing hypoxia-stimulated up-regulation of acetate metabolism in tumor cells., Joint Molecular Imaging Conference},
 title = {Is acetate metabolism a possible imaging marker for hypoxia-stimulating tumors?},
 year = {2007}
}