Accumulation of trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid in prostate cancer due to androgen-induced expression of amino acid transporters

Mol Imaging Biol. 2014 Dec;16(6):756-64. doi: 10.1007/s11307-014-0756-x.

Abstract

Purpose: 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).

Procedures: 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.

MeSH terms

  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism*
  • Androgens / metabolism
  • Anilides / pharmacology
  • Carboxylic Acids / analysis
  • Carboxylic Acids / pharmacokinetics*
  • Cell Line, Tumor
  • Cyclobutanes / analysis
  • Cyclobutanes / pharmacokinetics*
  • Dihydrotestosterone / pharmacology*
  • Fluorine Radioisotopes
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Nitriles / pharmacology
  • Prostatic Neoplasms, Castration-Resistant / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant / metabolism*
  • Radioactive Tracers
  • Radionuclide Imaging
  • Radiopharmaceuticals / analysis
  • Radiopharmaceuticals / pharmacokinetics*
  • Receptors, Androgen / metabolism
  • Tosyl Compounds / pharmacology

Substances

  • AR protein, human
  • Amino Acid Transport Systems
  • Androgens
  • Anilides
  • Carboxylic Acids
  • Cyclobutanes
  • Fluorine Radioisotopes
  • Nitriles
  • Radioactive Tracers
  • Radiopharmaceuticals
  • Receptors, Androgen
  • Tosyl Compounds
  • Dihydrotestosterone
  • fluciclovine F-18
  • bicalutamide