title: Relationship between [14C]MeAIB uptake and amino acid transporter family gene expression levels or proliferative activity in a pilot study in human carcinoma cells: Comparison with [3H]methionine uptake.
abstract: BACKGROUND
  To clarify the difference between system A and L amino acid transport imaging in PET clinical imaging, we focused on the use of α-[N-methyl-11C]-methylaminoisobutyric acid ([11C]MeAIB), and compared it with [S-methyl-11C]-L-methionine ([11C]MET). The aim of this study was to assess the correlation of accumulation of these two radioactive amino acid analogs with expression of amino acid transporters and cell proliferative activity in carcinoma cells.
  
  
  METHODS
  Amino acid uptake inhibitor studies were performed in four human carcinoma cells (epidermal carcinoma A431, colorectal carcinoma LS180, and lung carcinomas PC14/GL and H441/GL) using the radioisotope analogs [3H]MET and [14C]MeAIB. MeAIB was used to inhibit the A system and 2-amino-2-norbornane-carboxylic acid (BCH) was used to inhibit the L system. The carcinoma gene expression levels of a number of amino acid transporters were measured by microarray and quantitative polymerase chain reaction. Carcinoma proliferative activity was assessed using accumulation of [methyl-3H]-3'-deoxy-3'-fluorothymidine ([3H]FLT).
  
  
  CONCLUSIONS
  [14C]MeAIB uptake occurred principally via a Na+-dependent A type mechanism whereas [3H]MET uptake occurred predominantly via a Na+-independent L type mechanism although other transporters were also utilized depending on cell type. There was no correlation between [3H]MET uptake and total system L amino acid transporter (LAT) expression. In contrast, [14C]MeAIB uptake strongly correlated with total system A amino acid transporter (SNAT) expression and proliferative activity in this preliminary study using four human carcinoma cell lines. Carcinoma proliferative activity also correlated with total SNAT expression. Advances in Knowledge and Implications for Patient Care: Because there is a significant correlation between the accumulation of [14C]MeAIB and the gene expression level of total SNAT as well as the accumulation of [3H]FLT, it is suggested that use of the analog [11C]MeAIB in PET may provide an indication of tumor cell proliferative activity. [11C]MeAIB is therefore expected to be very useful in PET imaging.
authors.affiliation: Division of PET Imaging, Shiga Medical Center Research Institute, Shiga, Japan; Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kagawa
authors.affiliation: Division of PET Imaging, Shiga Medical Center Research Institute, Shiga, Japan; Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishii
authors.affiliation: Division of PET Imaging, Shiga Medical Center Research Institute, Shiga, Japan; Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Division of PET Imaging, Shiga Medical Center Research Institute, Shiga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamauchi
authors.affiliation: Department of Radiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okudaira
authors.affiliation: Wellness Promotion Science Center, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Division of Functional Imaging, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yoshimoto
authors.affiliation: Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Shikano
authors.affiliation: Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan. Electronic address: kei@mhs.mp.kanazawa-u.ac.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawai
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics*; D001692:Biological Transport; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008715:Methionine / Q000378:metabolism*; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D026905:Amino Acid Transport Systems; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; D008715:Methionine
keywords: Amino acid transporters; Flt; MeAIB; Met; Proliferative activity; System A