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This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yoshii, Y. Articles by Fujibayashi, Y. PubMed Articles by Yoshii, Y. Articles by Fujibayashi, Y.

Tumor acetate imaging: A new paradigm for understanding tumor-specific hypoxic metabolism

¹ BIRC, Univ. Fukui, Eiheiji, Japan; ² MIC, NIRS, Chiba, Japan

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Objectives: ¹¹C-acetate PET is traditionally used for myocardial studies. In myocardium, mitochondrial acetyl-CoA synthetase (Acss) 1 contributes to acetate tracer uptake. Meanwhile, the ¹¹C-acetate PET is used for tumor diagnosis; however, the exact mechanism has been unclear. From our data, tumor cells expressed cytosolic Acss2, but not Acss1. In tumor cells, Acss2 was up-regulated under hypoxia and able to mediate an acetate-producing pathway with energy synthesis, which suggests that Acss2 would control both anabolism and catabolism of acetate coordinately. In this study, we examined a role of Acss2 in tumor acetate tracer uptake and considered a possibility of acetate imaging for visualizing tumor hypoxic metabolism.

Methods: Four mouse tumor cell lines (LLC1, B16, Colon-26, C127I) and a fibroblast cell line as control were used. To suppress Acss2, RNAi was performed. For ¹⁴C-acetate uptake study, cells were preincubated and some cells were treated by 2 h hypoxia, additionally. Cells were incubated in medium containing 37kBq ¹⁴C-acetate for 1 h under the same condition. Then, radioactivity was measured.

Results: In tumor cells, ¹⁴C-acetate uptake was increased under hypoxia than normoxia, but not in control. The pattern of ¹⁴C-acetate uptake was mostly correlated to Acss2 expression pattern. In Acss2 RNAi tumor cells, ¹⁴C-acetate uptake was decreased, regardless of O₂ conditions, compared with control RNAi. This implicated that Acss2 participated in acetate tracer uptake in tumor cells.

Conclusions: We found that Acss2 plays significant roles in acetate tracer uptake in tumor cells, indicating that tumor cells possess a different acetate uptake mechanism from that in myocardium. These evidences suggest that acetate imaging can reflect a tumor-specific acetate metabolism activated under hypoxia.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yoshii, Y. Articles by Fujibayashi, Y. PubMed Articles by Yoshii, Y. Articles by Fujibayashi, Y.