Sho Koyasu1,2,3, Yoichi Shimizu4, Akiyo Morinibu5, Tsuneo Saga4, Yuji Nakamoto4, Kaori Togashi4, Hiroshi Harada5. 1. Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. sho@kuhp.kyoto-u.ac.jp. 2. Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan. sho@kuhp.kyoto-u.ac.jp. 3. Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan. sho@kuhp.kyoto-u.ac.jp. 4. Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. 5. Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Abstract
PURPOSE: Recently, the potential value of isocitrate dehydrogenase (IDH) mutation as a prognostic marker in glioblastomas has been established. Glioblastomas are classified by their IDH mutation status under the 2016 WHO classification system. However, noninvasive diagnostic methods for the mutation status in glioblastoma patients have not been established so far. The purpose of this study was to evaluate the difference of acetate metabolism between in glioblastomas with wild-type IDH and in those with IDH mutation by comparing the uptake of 14C-acetate using genetically engineered glioblastoma cell lines in vitro and in vivo. METHODS: We established glioblastoma cells (U251) expressing IDH1 R132H and examined the cell uptake of [1-14C]acetate. Biodistribution studies and an autoradiographic study for U251 cell tumor-bearing mice (BALB/c-nu/nu) with or without the IDH1 mutation were performed 1 h after [1-14C]acetate administration. RESULTS: Significantly higher uptake of [1-14C]acetate was observed in U251/IDH1 R132H cells than in U251/IDH1 wild-type cells both in vitro (10.11 ± 0.94 vs. 4.26 ± 0.95%dose/mg, p = 0.0047) and in vivo (0.97 ± 0.14 vs. 0.66 ± 0.05%ID/g; p = 0.0037). Tumor-to-muscle ratios were also significantly higher in U251/IDH1 R132H tumors (3.36 ± 0.41 vs. 1.88 ± 0.59, p = 0.0030). The autoradiographic study shows the entirely higher radioactivity of the U251/IDH1 R132H tumor tissue section than that of the U251/IDH1 Wild-type tumor. CONCLUSIONS: In vitro and in vivo studies demonstrated that the uptake of radiolabeled acetate was significantly higher in IDH-mutated cells than in IDH-wild-type cells.
PURPOSE: Recently, the potential value of isocitrate dehydrogenase (IDH) mutation as a prognostic marker in glioblastomas has been established. Glioblastomas are classified by their IDH mutation status under the 2016 WHO classification system. However, noninvasive diagnostic methods for the mutation status in glioblastomapatients have not been established so far. The purpose of this study was to evaluate the difference of acetate metabolism between in glioblastomas with wild-type IDH and in those with IDH mutation by comparing the uptake of 14C-acetate using genetically engineered glioblastoma cell lines in vitro and in vivo. METHODS: We established glioblastoma cells (U251) expressing IDH1 R132H and examined the cell uptake of [1-14C]acetate. Biodistribution studies and an autoradiographic study for U251 cell tumor-bearing mice (BALB/c-nu/nu) with or without the IDH1 mutation were performed 1 h after [1-14C]acetate administration. RESULTS: Significantly higher uptake of [1-14C]acetate was observed in U251/IDH1 R132H cells than in U251/IDH1 wild-type cells both in vitro (10.11 ± 0.94 vs. 4.26 ± 0.95%dose/mg, p = 0.0047) and in vivo (0.97 ± 0.14 vs. 0.66 ± 0.05%ID/g; p = 0.0037). Tumor-to-muscle ratios were also significantly higher in U251/IDH1 R132Htumors (3.36 ± 0.41 vs. 1.88 ± 0.59, p = 0.0030). The autoradiographic study shows the entirely higher radioactivity of the U251/IDH1 R132Htumor tissue section than that of the U251/IDH1 Wild-type tumor. CONCLUSIONS: In vitro and in vivo studies demonstrated that the uptake of radiolabeled acetate was significantly higher in IDH-mutated cells than in IDH-wild-type cells.
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