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


METHODS
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.


RESULTS
(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.


CONCLUSIONS
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.
School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-0942, Japan.
Masato
M
Kobayashi
Fumiya
F
Hashimoto
Kazuyo
K
Ohe
Takahiro
T
Nadamura
Kodai
K
Nishi
Naoto
N
Shikano
Ryuichi
R
Nishii
Tatsuya
T
Higashi
Hidehiko
H
Okazawa
Keiichi
K
Kawai
D026905:Amino Acid Transport Systems / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes / Q000737:chemistry; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007553:Isotope Labeling; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D051379:Mice; D013237:Stereoisomerism; D014316:Tritium / Q000737:chemistry
D026905:Amino Acid Transport Systems; D002250:Carbon Radioisotopes; D014316:Tritium; D008715:Methionine