Differences in Accumulation and the Transport Mechanism of l - and d -Methionine in High- and Low-Grade Human Glioma Cells

• Published in: Nuclear medicine and biology Vol. 44; pp. 78 - 82
• Main Authors: Kobayashi, Masato, Mizutani, Asuka, Nishi, Kodai, Nakajima, Syuichi, Shikano, Naoto, Nishii, Ryuichi, Fukuchi, Kazuki, Kawai, Keiichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2017
• Subjects: Amino acid transport system; Amino Acid Transport Systems - metabolism; Biological Transport; Carbon Radioisotopes; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Glioma; Glioma - metabolism; Glioma - pathology; Humans; Methionine; Methionine - chemistry; Methionine - metabolism; Neoplasm Grading; Positron emission tomography; Radiology; Stereoisomerism; Glioma; Amino acid transport system; positron emission tomography; Methionine; Positron emission tomography
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2016.09.003

Abstract Introduction Although [S-methyl-11C]-labeled L- and D-methionine (11 C-L- and 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 of11 C-D-MET and11 C-L-MET are the same.11 C-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-3 H]-L-MET (3 H-L-MET) and [S-methyl-3 H]-D-MET (3 H-D-MET) in these cells was compared during 60 min of incubation. The transport mechanism of3 H-L-MET and3 H-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.3 H-D-MET, which is transported by systems L and ASC, accumulated at higher levels than3 H-L-MET at all incubation times because3 H-D-MET is more sensitive to system ASC than3 H-L-MET. Conversely, in low-grade glioma cells with lower expression of system L and ASC,3 H-D-MET accumulated at higher levels than3 H-L-MET in early incubation times because3 H-D-MET may be more sensitive to system ASC than system L. Conclusion3 H-D-MET was mainly transported by systems L and ASC and sensitive to system ASC, whereas3 H-L-MET was transported by system L in human glioma cells. In vitro, the accumulation of3 H-D-MET was significantly higher than that of3 H-L-MET during the entire incubation time in high-grade glioma cells, and in early incubation times in low-grade glioma cells.