Transport mechanism of (11)C-labeled L- and D-methionine in human-derived tumor cells

• Published in: Nuclear medicine and biology 2012-11, Vol.39 (8), p.1213-1218
• Main Authors: Kobayashi, Masato, Hashimoto, Fumiya, Ohe, Kazuyo, Nadamura, Takahiro, Nishi, Kodai, Shikano, Naoto, Nishii, Ryuichi, Higashi, Tatsuya, Okazawa, Hidehiko, Kawai, Keiichi
• Format: Article
• Language: English
• Subjects: Amino Acid Transport Systems - metabolism; Animals; Biological Transport; Carbon Radioisotopes - chemistry; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Isotope Labeling; Kidney - metabolism; Liver - metabolism; Male; Methionine - chemistry; Methionine - metabolism; Methionine - pharmacokinetics; Mice; Stereoisomerism; Tritium - chemistry
• ISSN: 1872-9614
• DOI: 10.1016/j.nucmedbio.2012.06.006

S-methyl-(11)C-labeled l- and d-methionine ((11)C-l- and d-MET) are useful as radiotracers for tumor imaging. However, it is not known whether the transport mechanism of (11)C-d-MET is the same as that for (11)C-l-MET, which is transported by the amino acid transport system L. In this study, we investigated the transport mechanism of (11)C-l- and d-MET by analyzing the expression of transport system genes in human-derived tumor cells. The expression of transport system genes in human-derived tumor cells was quantitatively analyzed. The mechanism of MET transport in these cells was investigated by incubating the cells with [S-methyl-(3)H]-l-MET ((3)H-l-MET) or [S-methyl-(3)H]-d-MET ((3)H-d-MET) and the effect of 2-amino-2- norbornane-carboxylic acid, a system L transport inhibitor, or α-(methylamino)isobutyric acid, a system A transport inhibitor, on their transport was measured. The transport and metabolic stability of [S-methyl-(14)C]-l-MET ((14)C-l-MET) and (3)H-d-MET was also analyzed using bearing mice with H441 or PC14 tumor cells. (3)H-d-MET was mainly transported by both systems L and alanine-serine-cysteine (ASC), while system L was involved in (3)H-l-MET transport. There was a high correlation between both (3)H-l-MET and (3)H-d-MET uptake and the expression of amino acid transport system genes. In the in vivo study, H441-cell accumulation of (3)H-d-MET was higher than that of (14)C-l-MET. Hepatic and renal accumulation of (3)H-d-MET was lower than that of (14)C-l-MET. The transport mechanism of (3)H-d-MET was different from that of (3)H-l-MET. Since (3)H-d-MET has high metabolic stability, its accumulation reflects the transporter function of system L and ASC.