title: Transport of 3-fluoro-L-α-methyl-tyrosine (FAMT) by organic ion transporters explains renal background in [(18)F]FAMT positron emission tomography.
abstract: A PET tracer for tumor imaging, 3-(18)F-l-α-methyl-tyrosine ([(18)F]FAMT), has advantages of high cancer-specificity and low physiological background. In clinical studies, FAMT-PET has been proved useful for the detection of malignant tumors and their differentiation from inflammation and benign lesions. The tumor specific uptake of FAMT is due to its high-selectivity to cancer-type amino acid transporter LAT1 among amino acid transporters. In [(18)F]FAMT PET, kidney is the only organ that shows high physiological background. To reveal transporters involved in renal accumulation of FAMT, we have examined [(14)C]FAMT uptake on the organic ion transporters responsible for the uptake into tubular epithelial cells. We have found that OAT1, OAT10 and OCTN2 transport [(14)C]FAMT. The [(14)C]FAMT uptake was inhibited by probenecid, furosemide and ethacrynic acid, consistent with the properties of the transporters. The amino acid uptake inhibitor, 2-amino-2-norbornanecarboxylic acid (BCH), also inhibited the [(14)C]FAMT uptake, whereas OCTN2-mediated [(14)C]FAMT uptake was Na(+)-dependent. We propose that FAMT uptake by OAT1, OAT10 and OCTN2 into tubular epithelial cells could contribute to the renal accumulation of FAMT. The results from this study would provide clues to the treatments to reduce renal background and enhance tumor uptake as well as to designing PET tracers with less renal accumulation.
authors.affiliation: Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.affiliation: Advanced Clinical Research Center, Fukushima Medical University, Fukushima, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tominaga
authors.affiliation: Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Ohgaki
authors.affiliation: Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Pattama
authors.initials: P
authors.lastname: Wiriyasermkul
authors.affiliation: Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hagiwara
authors.affiliation: Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Okuda
authors.affiliation: Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.affiliation: Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Advanced Clinical Research Center, Fukushima Medical University, Fukushima, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Oriuchi
authors.affiliation: Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Shushi
authors.initials: S
authors.lastname: Nagamori
authors.affiliation: Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. Electronic address: ykanai@pharma1.med.osaka-u.ac.jp.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism*; D008781:Methyltyrosines / Q000378:metabolism; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D027362:Organic Anion Transport Protein 1 / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000378:metabolism; D000074058:Solute Carrier Family 22 Member 5; D014982:Xenopus laevis
chemical_list: D005462:Fluorine Radioisotopes; D027283:Large Neutral Amino Acid-Transporter 1; D008781:Methyltyrosines; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D019275:Radiopharmaceuticals; C530205:SLC22A13 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5
keywords: Epithelial transport; Kidney; Organic anion; PET tracer; Transporter