title: Kinetic analyses of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid transport in Xenopus laevis oocytes expressing human ASCT2 and SNAT2.
abstract: BACKGROUND
  Trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18)F]FACBC) is a promising amino acid positron emission tomography (PET) radiotracer for visualizing prostate cancer. We previously showed that anti-FACBC is transported by amino acid transporters, especially by alanine-serine-cysteine transporter 2 (ASCT2), which is associated with tumor growth. We studied this affinity to assess the mechanism of anti-FACBC transport in prostate cancer cells.
  
  
  METHODS
  Kinetic assays for trans-1-amino-3-fluoro-[1-(14)C]cyclobutanecarboxylic acid ([(14)C]FACBC) were performed in Xenopus laevis oocytes over-expressing either ASCT2 or sodium-coupled neutral amino acid transporter 2 (SNAT2), both of which are highly expressed in prostate cancer cells. We also examined the kinetics of [(14)C]FACBC uptake using mammalian cell lines over-expressing system L amino acid transporter 1 or 2 (LAT1 or LAT2). Results: ASCT2 and SNAT2 transported [14C]FACBC with Michaelis–Menten kinetics Km values of 96.7 ± 45.2 μM and 196.5 ± 19.7 μM, respectively. [correted]. LAT1 and LAT2 transported [(14)C]FACBC with Michaelis-Menten Km values of 230.4 ± 184.5 μM and 738.5 ± 87.6 μM, respectively.
  
  
  CONCLUSIONS
  Both ASCT2 and SNAT2 recognize anti-FACBC as a substrate. Anti-FACBC has higher affinity for ASCT2 than for SNAT2, LAT1, or LAT2. The ASCT2-preferential transport of anti-[(18)F]FACBC in cancer cells could be used for more effective prostate cancer imaging.
authors: Graduate School of Medical Science, Kanazawa University, Ishikawa 920-0942, Japan. hiroyuki_okudaira@nmp.co.jp
authors: Hiroyuki
authors: H
authors: Okudaira
authors: Takeo
authors: T
authors: Nakanishi
authors: Shuntaro
authors: S
authors: Oka
authors: Masato
authors: M
authors: Kobayashi
authors: Hiroshi
authors: H
authors: Tamagami
authors: David M
authors: DM
authors: Schuster
authors: Mark M
authors: MM
authors: Goodman
authors: Yoshifumi
authors: Y
authors: Shirakami
authors: Ikumi
authors: I
authors: Tamai
authors: Keiichi
authors: K
authors: Kawai
mesh_terms: D026924:Amino Acid Transport System A / Q000235:genetics* / Q000378:metabolism*; D026962:Amino Acid Transport System ASC / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002264:Carboxylic Acids / Q000378:metabolism*; D002460:Cell Line; D003503:Cyclobutanes / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D051379:Mice; D015778:Minor Histocompatibility Antigens; D009865:Oocytes / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics*
chemical_list: D026924:Amino Acid Transport System A; D026962:Amino Acid Transport System ASC; D002264:Carboxylic Acids; D003503:Cyclobutanes; D027283:Large Neutral Amino Acid-Transporter 1; D015778:Minor Histocompatibility Antigens; C420506:SLC1A5 protein, human; C498797:SLC38A2 protein, human; C117460:fluciclovine F-18