Specific transport of 3-fluoro-l-α-methyl-tyrosine by LAT1 explains its specificity to malignant tumors in imaging.
Bottom Line: Km of LAT1-mediated [14C]FAMT transport was 72.7 μM, similar to that for endogenous substrates.FAMT is highly specific to cancer-type amino acid transporter LAT1, which explains the cancer-specific accumulation of [18F]FAMT in PET.This, vice versa, further supports the cancer-specific expression of LAT1.
Affiliation: Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Japan.Show MeSH
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Mentions: Among the transporters from system L for large neutral amino acids, LAT1‐expressing oocytes exhibited a high level of [14C]FAMT uptake compared with control oocytes (Fig. 1a). Its transport rate was comparable to that of l‐[14C]leucine, a typical substrate of LAT1. LAT2, LAT3 and LAT4 did not mediate [14C]FAMT transport (Fig. 1b–d). In contrast, l‐[14C]methionine was transported by all the system L transporters (Fig. 1). Other amino acid transporters transporting aromatic amino acids, TAT1, B0AT1, ATB0,+, b0,+, y+LAT1 and y+LAT2, did not transport [14C]FAMT, whereas these transporters except TAT1 transported l‐[14C]methionine (Fig. 2). The transporters for small neutral amino acids, ASCT1, ASCT2, SNAT1, SNAT2, SNAT3, SNAT4 and SNAT5, did not transport [14C]FAMT, whereas l‐[14C]methionine was transported by all except ASCT1 (Fig. S2). The results on the amino acid transporters are summarized in Table 1.
Affiliation: Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Japan.