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

• Type of Material: Article
• Authors: Hiroyuki Okudaira, Nihon Medi-Physics Co., Ltd.; Shuntaro Oka, Nihon Medi-Physics Co., Ltd.; Masahiro Ono, Nihon Medi-Physics Co., Ltd.; Takeo Nakanishi, Kanazawa University; David Schuster, Emory University; Masato Kobayashi, Kanazawa University; Mark Goodman, Emory University; Ikumi Tamai, Kanazawa University; Keiichi Kawai, Kanazawa University; Yoshifumi Shirakami, Nihon Medi-Physics Co., Ltd.
• Language: English
• Date: 2014-12-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014, Academy of Molecular Imaging and Society for Molecular Imaging.
• Final Published Version (URL): http://dx.doi.org/10.1007/s11307-014-0756-x
• Title of Journal or Parent Work: Molecular Imaging and Biology
• ISSN: 1536-1632
• Volume: 16
• Issue: 6
• Start Page: 756
• End Page: 764
• Keywords: MECHANISMS; PROGRESSION; CARCINOMA; ASCT2; Science & Technology; anti-FACBC; Radiology, Nuclear Medicine & Medical Imaging; Life Sciences & Biomedicine; Androgen; Prostate cancer; ANTI-1-AMINO-3-F-18-FLUOROCYCLOBUTANE-1-CARBOXYLIC ACID; RECEPTOR; LAT1; CELL-GROWTH; PET/CT; Amino acid transporter; IDENTIFICATION
• Research Categories: Health Sciences, Pharmacy; Health Sciences, Oncology

Abstract

Purpose: Androgens play a crucial role in prostate cancer progression, and trans-1-amino-3-[ < sup > 18 < /sup > F]fluorocyclobutanecarboxylic acid (anti-[ < sup > 18 < /sup > F]FACB C) are used for visualization of prostate cancer. We examined the effect of androgen on the expression of amino acid transporters related to anti-[ < sup > 18 < /sup > F]FACBC transport and uptake of trans-1-amino-3-fluoro-[1- < sup > 14 < /sup > C]cyclobutanecarboxylic acid (anti-[ < sup > 14 < /sup > C]FACBC). Procedures: Expression of amino acid transporters and uptake of anti-[ < sup > 14 < /sup > 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-[ < sup > 14 < /sup > 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-[ < sup > 18 < /sup > F]FACBC uptake, thereby increasing anti-[ < sup > 14 < /sup > C]FACBC uptake in AR-positive LNCaP cells. Androgen-mediated induction may contribute to the distinct anti-[ < sup > 18 < /sup > F]FACBC accumulation pattern in prostate cancer.