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).
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.
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.
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.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90
Jadvar H (2011) Prostate cancer: PET with 18 F-FDG, 18 F- or 11C-acetate, and 18 F- or 11C-choline. J Nucl Med 52:81–89
Jadvar H, Desai B, Ji L et al (2013) Baseline 18 F-FDG PET/CT parameters as imaging biomarkers of overall survival in castrate-resistant metastatic prostate cancer. J Nucl Med 54:1195–1201
Jadvar H (2013) Molecular imaging of prostate cancer with PET. J Nucl Med 54:1685–1688
Schuster DM, Votaw JR, Nieh PT et al (2007) Initial experience with the radiotracer anti-1-amino-3-18 F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma. J Nucl Med 48:56–63
Schuster DM, Savir-Baruch B, Nieh PT et al (2011) Detection of recurrent prostate carcinoma with anti-1-amino-3-18 F-fluorocyclobutane-1-carboxylic acid PET/CT and 111In-capromab pendetide SPECT/CT. Radiology 259:852–861
Schuster DM, Nieh PT, Jani AB et al (2014) Anti-3-[18 F]FACBC positron emission tomography-computerized tomography and 111In-capromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial. J Urol 191:1446–1453
Asano Y, Inoue Y, Ikeda Y et al (2011) Phase I clinical study of NMK36: a new PET tracer with the synthetic amino acid analogue anti-[18 F]FACBC. Ann Nucl Med 25:414–418
Okudaira H, Shikano N, Nishii R et al (2011) Putative transport mechanism and intracellular fate of trans-1-amino-3-18 F-fluorocyclobutanecarboxylic acid in human prostate cancer. J Nucl Med 52:822–829
Oka S, Okudaira H, Yoshida Y, Schuster DM, Goodman MM, Shirakami Y (2012) Transport mechanisms of trans-1-amino-3-fluoro[1-14C]cyclobutanecarboxylic acid in prostate cancer cells. Nucl Med Biol 39:109–119
Okudaira H, Nakanishi T, Oka S et al (2013) Kinetic analyses of trans-1-amino-3-[18 F]fluorocyclobutanecarboxylic acid transport in Xenopus laevis oocytes expressing human ASCT2 and SNAT2. Nucl Med Biol 40:670–675
Ganapathy V, Thangaraju M, Prasad PD (2009) Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther 121:29–40
Nakanishi T, Tamai I (2011) Solute carrier transporters as targets for drug delivery and pharmacological intervention for chemotherapy. J Pharm Sci 100:3731–3750
Feldman BJ, Feldman D (2001) The development of androgen-independent prostate cancer. Nat Rev Cancer 1:34–45
Taplin ME, Balk SP (2004) Androgen receptor: a key molecule in the progression of prostate cancer to hormone independence. J Cell Biochem 91:483–490
Dutt SS, Gao AC (2009) Molecular mechanisms of castration-resistant prostate cancer progression. Future Oncol 5:1403–1413
Arakawa H, Nakanishi T, Yanagihara C et al (2012) Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions. Biochem Pharmacol 84:1070–1077
Trapman J, Cleutjens KB (1997) Androgen-regulated gene expression in prostate cancer. Semin Cancer Biol 8:29–36
Wang Q, Bailey CG, Ng C et al (2011) Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression. Cancer Res 71:7525–7536
Chuaqui RF, Englert CR, Strup SE et al (1997) Identification of a novel transcript up-regulated in a clinically aggressive prostate carcinoma. Urology 50:302–307
Babu E, Kanai Y, Chairoungdua A et al (2003) Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters. J Biol Chem 278:43838–43845
Chauvin TR, Griswold MD (2004) Androgen-regulated genes in the murine epididymis. Biol Reprod 71:560–569
Wang Q, Tiffen J, Bailey CG et al (2013) Targeting amino acid transport in metastatic castration-resistant prostate cancer: effects on cell cycle, cell growth, and tumor development. J Natl Cancer Inst 105:1463–1473
Janssen T, Raviv G, Camby I et al (1995) In-vitro characterization of dihydrotestosterone-induced, epidermal growth factor-induced and basic fibroblastic growth factor-induced modifications in the growth dynamics of the human prostate-cancer cell-line LNCaP, DU145 and PC3. Int J Oncol 7:1219–1225
Cantor JM, Ginsberg MH (2012) CD98 at the crossroads of adaptive immunity and cancer. J Cell Sci 125:1373–1382
Yanagida O, Kanai Y, Chairoungdua A et al (2001) Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta 1514:291–302
Todorova VK, Kaufmann Y, Luo S, Klimberg VS (2011) Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake. Cancer Chemother Pharmacol 67:285–291
Amaral JS, Pinho MJ, Soares-da-Silva P (2008) Genomic regulation of intestinal amino acid transporters by aldosterone. Mol Cell Biochem 313:1–10
Wolfgang CL, Lin C, Meng Q, Karinch AM, Vary TC, Pan M (2003) Epidermal growth factor activation of intestinal glutamine transport is mediated by mitogen-activated protein kinases. J Gastrointest Surg 7:149–156
Wise DR, DeBerardinis RJ, Mancuso A et al (2008) Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 105:18782–18787
Fuchs BC, Bode BP (2005) Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin Cancer Biol 15:254–266
Schwarzenböck S, Souvatzoglou M, Krause BJ (2012) Choline PET and PET/CT in primary diagnosis and staging of prostate cancer. Theranostics 2:318–330
Nanni C, Schiavina R, Boschi S et al (2013) Comparison of 18 F-FACBC and 11C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary results. Eur J Nucl Med Mol Imaging 40:S11–S17
Galsky MD, Small AC, Tsao CK, Oh WK (2012) Clinical development of novel therapeutics for castration-resistant prostate cancer: historic challenges and recent successes. CA Cancer J Clin 62:299–308
Shafi AA, Yen AE, Weigel NL (2013) Androgen receptors in hormone-dependent and castration-resistant prostate cancer. Pharmacol Ther 140:223–238
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.
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
(DOCX 32.6 kb)
About this article
Cite this article
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
- Prostate cancer
- Amino acid transporter