Differences in accumulation and the transport mechanism of l- and d-methionine in high- and low-grade human glioma cells.
Although [S-methyl-11C]-labeled L-methionine and D-methionine (11C-L-MET and11C-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 of11C-D-MET and11C-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.



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 of3H-L-MET and3H-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.



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 than3H-L-MET at all incubation times because3H-D-MET is more sensitive to system ASC than3H-L-MET. Conversely, in low-grade glioma cells with lower expression of system L and ASC,3H-D-MET accumulated at higher levels than3H-L-MET in early incubation times because3H-D-MET may be more sensitive to system ASC than system L.



3H-D-MET was mainly transported by systems L and ASC and sensitive to system ASC, whereas3H-L-MET was transported by system L in human glioma cells. In vitro, the accumulation of3H-D-MET was significantly higher than that of3H-L-MET during the entire incubation time in high-grade glioma cells, and in early incubation times in low-grade glioma cells.
Wellness Promotion Science Center, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan. Electronic address: kobayasi@mhs.mp.kanazawa-u.ac.jp.
Masato
M
Kobayashi
Graduate School of Medicine, Division of Health Sciences, Osaka University, Japan; Department of Radiology, Kanazawa University Hospital, Japan.
Asuka
A
Mizutani
Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
Kodai
K
Nishi
Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Japan.
Syuichi
S
Nakajima
Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Japan.
Naoto
N
Shikano
Molecular Imaging Center, National Institute of Radiological Sciences, Japan.
Ryuichi
R
Nishii
Graduate School of Medicine, Division of Health Sciences, Osaka University, Japan.
Kazuki
K
Fukuchi
School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan; Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
Keiichi
K
Kawai
D026905:Amino Acid Transport Systems / Q000378:metabolism; D001692:Biological Transport; D002250:Carbon Radioisotopes; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008715:Methionine / Q000737:chemistry* / Q000378:metabolism*; D060787:Neoplasm Grading; D049268:Positron-Emission Tomography; D013237:Stereoisomerism
D026905:Amino Acid Transport Systems; D002250:Carbon Radioisotopes; D008715:Methionine
Amino acid transport system; Glioma; Methionine; Positron emission tomography