Accumulation of Trans-1-Amino-3-[18F]Fluorocyclobutanecarboxylic Acid in Prostate Cancer due to Androgen-Induced Expression of Amino Acid Transporters

Androgens play a crucial role in prostate cancer progression, and trans-1-amino-3-[F-18]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-[F-18]FACBC transport and uptake of trans-1-amino-3-fluoro-[1-C-14]cyclobutanecarboxylic acid (anti-[C-14]FACBC). Expression of amino acid transporters and uptake of anti-[C-14]FACBC in androgen receptor (AR)-positive LNCaP and AR-negative DU145 human prostate cancer cells cultured with/without 5 alpha-dihydrotestosterone (DHT) and the effect of bicalutamide, an AR antagonist, on DHT-associated changes were investigated. DHT stimulated the expression of amino acid transporters ASCT2, SNAT5, 4F2 heavy chain, and LAT3 in LNCaP but not in DU145 cells. Anti-[C-14]FACBC uptake was enhanced, in a DHT-dependent manner, in LNCaP cells only. DHT enhanced the expression of ASCT2, the transporter responsible for anti-[F-18]FACBC uptake, thereby increasing anti-[C-14]FACBC uptake in AR-positive LNCaP cells. Androgen-mediated induction may contribute to the distinct anti-[F-18]FACBC accumulation pattern in prostate cancer.