RRC ID 11038
著者 Yoshii Y, Waki A, Furukawa T, Kiyono Y, Mori T, Yoshii H, Kudo T, Okazawa H, Welch MJ, Fujibayashi Y.
タイトル Tumor uptake of radiolabeled acetate reflects the expression of cytosolic acetyl-CoA synthetase: implications for the mechanism of acetate PET.
ジャーナル Nucl Med Biol
Abstract INTRODUCTION:[1-(11)C]Acetate positron emission tomography (PET) is used for myocardial studies. In the myocardium, mitochondrial acetyl-CoA synthetase (ACSS1) mainly contributes to the radiopharmaceutical uptake. [1-(11)C]Acetate PET is also used for tumor diagnosis; however, the uptake mechanism of radiolabeled acetate in tumors remains unclear. Our previous study reported that cytosolic acetyl-CoA synthetase (ACSS2) was expressed in tumor cells and up-regulated under hypoxia, whereas expression of ACSS1 was negligible regardless of the oxygen conditions. We also indicated that ACSS2 is a bidirectional enzyme that controls acetyl-CoA/acetate metabolism in tumor cells. In this study, to elucidate the basic mechanism of tumor acetate uptake, we focused on ACSS2 and investigated the role of ACSS2 in the uptake of radiolabeled acetate in tumor cells.
METHODS:[1-(14)C]Acetate uptake and ACSS2 expression were examined in four tumor cell lines under normoxia or hypoxia. An ACSS2 knockdown study was also performed.
RESULTS:[1-(14)C]Acetate uptake was increased in the tumor cells under hypoxia. This pattern followed that of ACSS2 expression. The incorporated (14)C was mostly distributed in the lipid-soluble fractions, and this tendency increased under hypoxia. ACSS2 knockdown led to a corresponding reduction in [1-(14)C]acetate uptake in all tumor cell lines examined under normoxia and hypoxia.
CONCLUSIONS:ACSS2 plays an important role in the uptake of radiolabeled acetate in tumor cells, which is different from that in the myocardium, which mainly involves ACSS1. The uptake of radiolabeled acetate in tumors increased under hypoxia along with up-regulation of ACSS2 expression. This suggests a possible mechanism for acetate PET for tumors.
巻・号 36(7)
ページ 771-7
公開日 2009-10-1
DOI 10.1016/j.nucmedbio.2009.05.006
PII S0969-8051(09)00150-4
PMID 19720289
MeSH Acetate-CoA Ligase / genetics Acetate-CoA Ligase / metabolism* Acetates / chemistry Acetates / metabolism* Animals Biological Transport Carbon Radioisotopes / chemistry Cell Hypoxia Cell Line, Tumor Cytosol / enzymology* Gene Expression Regulation, Neoplastic* Isotope Labeling Mice Neoplasms / diagnostic imaging* Neoplasms / genetics Neoplasms / metabolism* Neoplasms / pathology Positron-Emission Tomography Radioactivity Time Factors
IF 2.396
引用数 31
WOS 分野 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
リソース情報
ヒト・動物細胞 B16 melanoma(RCB1283)