Differences in Accumulation and the Transport Mechanism of l - and d -Methionine in High- and Low-Grade Human Glioma Cells
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....
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Published in | Nuclear medicine and biology Vol. 44; pp. 78 - 82 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.01.2017
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0969-8051 1872-9614 |
DOI: | 10.1016/j.nucmedbio.2016.09.003 |