Transport mechanism of 11C-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 system; Biological and medical sciences; Contrast media. Radiopharmaceuticals; Gene expression; Medical sciences; Methionine; PET; Pharmacology. Drug treatments; Tumor
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2012.06.006

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