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

Purpose

Androgens play a crucial role in prostate cancer progression, and trans-1-amino-3-¹⁸F]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-¹⁸F]FACBC transport and uptake of trans-1-amino-3-fluoro-1-¹⁴C]cyclobutanecarboxylic acid (anti-¹⁴C]FACBC).

Procedures

Expression of amino acid transporters and uptake of anti-¹⁴C]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-¹⁴C]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-¹⁸F]FACBC uptake, thereby increasing anti-¹⁴C]FACBC uptake in AR-positive LNCaP cells. Androgen-mediated induction may contribute to the distinct anti-¹⁸F]FACBC accumulation pattern in prostate cancer.