title: Accumulation of trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid in prostate cancer due to androgen-induced expression of amino acid transporters.
abstract: OBJECTIVE
  Androgens play a crucial role in prostate cancer progression, and trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18) F]FACBC) are used for visualization of prostate cancer. We examined the effect of androgen on the expression of amino acid transporters related to anti-[(18)F]FACBC transport and uptake of trans-1-amino-3-fluoro-[1-(14)C]cyclobutanecarboxylic acid (anti-[(14)C]FACBC).
  
  
  METHODS
  Expression of amino acid transporters and uptake of anti-[(14)C]FACBC in androgen receptor (AR)-positive LNCaP and AR-negative DU145 human prostate cancer cells cultured with/without 5α-dihydrotestosterone (DHT) and the effect of bicalutamide, an AR antagonist, on DHT-associated changes were investigated.
  
  
  RESULTS
  DHT stimulated the expression of amino acid transporters ASCT2, SNAT5, 4F2 heavy chain, and LAT3 in LNCaP but not in DU145 cells. Anti-[(14)C]FACBC uptake was enhanced, in a DHT-dependent manner, in LNCaP cells only.
  
  
  CONCLUSIONS
  DHT enhanced the expression of ASCT2, the transporter responsible for anti-[(18)F]FACBC uptake, thereby increasing anti-[(14)C]FACBC uptake in AR-positive LNCaP cells. Androgen-mediated induction may contribute to the distinct anti-[(18)F]FACBC accumulation pattern in prostate cancer.
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., 3-1 Kitasode, Sodegaura, Chiba, 299-0266, Japan, hiroyuki_okudaira@nmp.co.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okudaira
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Oka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Takeo
authors.initials: T
authors.lastname: Nakanishi
authors.forename: David M
authors.initials: DM
authors.lastname: Schuster
authors.forename: Masato
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Mark M
authors.initials: MM
authors.lastname: Goodman
authors.forename: Ikumi
authors.initials: I
authors.lastname: Tamai
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawai
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Shirakami
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D002264:Carboxylic Acids / Q000032:analysis / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003503:Cyclobutanes / Q000032:analysis / Q000493:pharmacokinetics*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005462:Fluorine Radioisotopes; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000000981:diagnostic imaging / Q000378:metabolism*; D011849:Radioactive Tracers; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000032:analysis / Q000493:pharmacokinetics*; D011944:Receptors, Androgen / Q000378:metabolism; D014105:Tosyl Compounds / Q000494:pharmacology
chemical_list: C410798:AR protein, human; D026905:Amino Acid Transport Systems; D000728:Androgens; D000813:Anilides; D002264:Carboxylic Acids; D003503:Cyclobutanes; D005462:Fluorine Radioisotopes; D009570:Nitriles; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D013196:Dihydrotestosterone; C117460:fluciclovine F-18; C053541:bicalutamide