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

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Abstract

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.

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Acknowledgments

We thank Ms. Sachiko Naito for her excellent technical assistance. We also thank Dr. Atsushi Mizokami for his helpful suggestions and comments regarding these experiments.

Conflict of Interest

Hiroyuki Okudaira, Shuntaro Oka, Masahiro Ono, and Yoshifumi Shirakami are employees of Nihon Medi-Physics Co., Ltd. Mark M. Goodman and Emory University have patent rights for anti-[18F]FACBC and are eligible to receive royalties on anti-[18F]FACBC from Nihon Medi-Physics Co., Ltd. Mark M. Goodman, David M. Schuster, and Keiichi Kawai have ongoing research collaborations with Nihon Medi-Physics Co., Ltd.

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Authors and Affiliations

  1. Research Center, Nihon Medi-Physics Co., Ltd., 3-1 Kitasode, Sodegaura, Chiba, 299-0266, Japan

    Hiroyuki Okudaira, Shuntaro Oka, Masahiro Ono & Yoshifumi Shirakami

  2. Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan

    Masahiro Ono, Masato Kobayashi & Keiichi Kawai

  3. Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Ishikawa, Japan

    Takeo Nakanishi & Ikumi Tamai

  4. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA

    David M. Schuster & Mark M. Goodman

  5. Biomedical Imaging Research Center, University of Fukui, Fukui, Japan

    Keiichi Kawai

Authors
  1. Hiroyuki Okudaira
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  2. Shuntaro Oka
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  3. Masahiro Ono
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  5. David M. Schuster
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  7. Mark M. Goodman
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  8. Ikumi Tamai
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Corresponding author

Correspondence to Hiroyuki Okudaira.

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Okudaira, H., Oka, S., Ono, M. et al. Accumulation of Trans-1-Amino-3-[18F]Fluorocyclobutanecarboxylic Acid in Prostate Cancer due to Androgen-Induced Expression of Amino Acid Transporters. Mol Imaging Biol 16, 756–764 (2014). https://doi.org/10.1007/s11307-014-0756-x

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