Masato Kobayashi1, Asuka Mizutani2, Kodai Nishi3, Syuichi Nakajima4, Naoto Shikano4, Ryuichi Nishii5, Kazuki Fukuchi6, Keiichi Kawai7. 1. Wellness Promotion Science Center, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan. Electronic address: kobayasi@mhs.mp.kanazawa-u.ac.jp. 2. Graduate School of Medicine, Division of Health Sciences, Osaka University, Japan; Department of Radiology, Kanazawa University Hospital, Japan. 3. Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan. 4. Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Japan. 5. Molecular Imaging Center, National Institute of Radiological Sciences, Japan. 6. Graduate School of Medicine, Division of Health Sciences, Osaka University, Japan. 7. School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan; Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
Abstract
INTRODUCTION: Although [S-methyl-11C]-labeled L-methionine and D-methionine (11C-L-MET and 11C-D-MET) are useful radiotracers for positron emission tomography imaging of brain tumors, it is not known whether the accumulation and transport mechanisms underlying uptake of 11C-D-MET and 11C-L-MET are the same. 11C-L-MET is mainly taken up by the amino acid transport system L. We evaluated accumulation and the transport mechanism of D-MET in high- and low-grade human glioma cells in vitro. METHODS: The expression of transport system genes in high- (A172 and T98G) and low-grade (SW1088 and Hs683) glioma cells was quantitatively analyzed. Accumulation of [S-methyl-3H]-L-MET (3H-L-MET) and [S-methyl-3H]-D-MET (3H-D-MET) in these cells was compared during 60min of incubation. The transport mechanism of 3H-L-MET and 3H-D-MET was investigated by incubating the cells with these compounds and examining the effect of the inhibitors 2-amino-2-norbornane-carboxylic acid or α-(methylamino) isobutyric acid. RESULTS: Absolute expression levels of system L and system alanine-serine-cysteine (ASC) in high-grade glioma cells were higher than in low-grade cells. In high-grade glioma cells, expression of system ASC genes was higher than that of system L genes. 3H-D-MET, which is transported by systems L and ASC, accumulated at higher levels than 3H-L-MET at all incubation times because 3H-D-MET is more sensitive to system ASC than 3H-L-MET. Conversely, in low-grade glioma cells with lower expression of system L and ASC, 3H-D-MET accumulated at higher levels than 3H-L-MET in early incubation times because 3H-D-MET may be more sensitive to system ASC than system L. CONCLUSION: 3H-D-MET was mainly transported by systems L and ASC and sensitive to system ASC, whereas 3H-L-MET was transported by system L in human glioma cells. In vitro, the accumulation of 3H-D-MET was significantly higher than that of 3H-L-MET during the entire incubation time in high-grade glioma cells, and in early incubation times in low-grade glioma cells.
INTRODUCTION: Although [S-methyl-11C]-labeled L-methionine and D-methionine (11C-L-MET and 11C-D-MET) are useful radiotracers for positron emission tomography imaging of brain tumors, it is not known whether the accumulation and transport mechanisms underlying uptake of 11C-D-MET and 11C-L-MET are the same. 11C-L-MET is mainly taken up by the amino acid transport system L. We evaluated accumulation and the transport mechanism of D-MET in high- and low-grade humanglioma cells in vitro. METHODS: The expression of transport system genes in high- (A172 and T98G) and low-grade (SW1088 and Hs683) glioma cells was quantitatively analyzed. Accumulation of [S-methyl-3H]-L-MET (3H-L-MET) and [S-methyl-3H]-D-MET (3H-D-MET) in these cells was compared during 60min of incubation. The transport mechanism of 3H-L-MET and 3H-D-MET was investigated by incubating the cells with these compounds and examining the effect of the inhibitors 2-amino-2-norbornane-carboxylic acid or α-(methylamino) isobutyric acid. RESULTS: Absolute expression levels of system L and system alanine-serine-cysteine (ASC) in high-grade glioma cells were higher than in low-grade cells. In high-grade glioma cells, expression of system ASC genes was higher than that of system L genes. 3H-D-MET, which is transported by systems L and ASC, accumulated at higher levels than 3H-L-MET at all incubation times because 3H-D-MET is more sensitive to system ASC than 3H-L-MET. Conversely, in low-grade glioma cells with lower expression of system L and ASC, 3H-D-MET accumulated at higher levels than 3H-L-MET in early incubation times because 3H-D-MET may be more sensitive to system ASC than system L. CONCLUSION:3H-D-MET was mainly transported by systems L and ASC and sensitive to system ASC, whereas 3H-L-MET was transported by system L in humanglioma cells. In vitro, the accumulation of 3H-D-MET was significantly higher than that of 3H-L-MET during the entire incubation time in high-grade glioma cells, and in early incubation times in low-grade glioma cells.
Authors: Javier Márquez; Francisco J Alonso; José M Matés; Juan A Segura; Mercedes Martín-Rufián; José A Campos-Sandoval Journal: Neurochem Res Date: 2017-03-09 Impact factor: 3.996
Authors: Pavithra Viswanath; Georgios Batsios; Joydeep Mukherjee; Anne Marie Gillespie; Peder E Z Larson; H Artee Luchman; Joanna J Phillips; Joseph F Costello; Russell O Pieper; Sabrina M Ronen Journal: Nat Commun Date: 2021-01-04 Impact factor: 14.919