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

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.

• Authors: Hiroyuki Okudaira, Shuntaro Oka, Masahiro Ono, Takeo Nakanishi, David M Schuster, Masato Kobayashi, Mark M Goodman, Ikumi Tamai, Keiichi Kawai, Yoshifumi Shirakami
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 16 Issue 6 Pg. 756-64 (Dec 2014) ISSN: 1860-2002 [Electronic] United States
• PMID: 24943499 (Publication Type: Journal Article)

Chemical References

• 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

Topics

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