title: Predominant contribution of L-type amino acid transporter to 4-borono-2-(18)F-fluoro-phenylalanine uptake in human glioblastoma cells.
abstract: BACKGROUND
  4-Borono-2-(18)F-fluoro-phenylalanine ((18)F-FBPA) has been used to anticipate the therapeutic effects of boron neutron capture therapy (BNCT) with 4-borono-L-phenylalanine (BPA). Similarly, L-[methyl-(11)C]-methionine ((11)C-MET), the most popular amino acid PET tracer, is a possible candidate for this purpose. We investigated the transport mechanism of (18)F-FBPA and compared it with that of (14)C-MET in human glioblastoma cell lines.
  
  
  METHODS
  Uptake of (18)F-FBPA and (14)C-MET was examined in A172, T98G, and U-87MG cells using 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid (a system L-specific substrate), 2-(methylamino)-isobutyric acid (a system A-specific substrate), and BPA. Gene expression was analyzed by quantitative real time polymerase chain reaction.
  
  
  RESULTS
  System L was mainly involved in the uptake of (18)F-FBPA (74.5%-81.1% of total uptake) and (14)C-MET (48.3%-59.4%). System A and ASC also contributed to the uptake of (14)C-MET. Inhibition experiments revealed that BPA significantly decreased the uptake of (18)F-FBPA, whereas 31%-42% of total (14)C-MET uptake was transported by BPA non-sensitive transporters. In addition, (18)F-FBPA uptake correlated with LAT1 and total LAT expressions.
  
  
  CONCLUSIONS
  This study demonstrated that (18)F-FBPA was predominantly transported by system L in human glioblastoma cells compared to (14)C-MET. Although further studies are needed to elucidate the correlation between (18)F-FBPA uptake and BPA content in tumor tissues, (18)F-FBPA is suitable for the selection of patients who benefit from BNCT with BPA.
authors.affiliation: Division of Functional Imaging, National Cancer Center Hospital East, Chiba. miyoshim@ncc.go.jp
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kurihara
authors.forename: Natsuki
authors.initials: N
authors.lastname: Honda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawai
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Ohe
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.forename: Jun
authors.initials: J
authors.lastname: Itami
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Arai
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001896:Boron Compounds / Q000378:metabolism* / Q000494:pharmacology; D016754:Boron Neutron Capture Therapy; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D049268:Positron-Emission Tomography
chemical_list: D026905:Amino Acid Transport Systems; D001896:Boron Compounds; C072915:4-borono-2-fluorophenylalanine; D010649:Phenylalanine; D008715:Methionine; C038344:methionine methyl ester; C033685:4-boronophenylalanine