Accumulation of trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid in prostate cancer due to androgen-induced expression of amino acid transporters.

Accumulation of trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid in prostate cancer due to androgen-induced expression of amino acid transporters.
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DOI:
10.1007/s11307-014-0756-x
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发表时间:
2014-12
影响因子:
3.1
通讯作者:
Shirakami Y
Shirakami Y
中科院分区:
医学3区
文献类型:
--
作者:
Okudaira H;Oka S;Ono M;Nakanishi T;Schuster DM;Kobayashi M;Goodman MM;Tamai I;Kawai K;Shirakami Y

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雄激素在前列腺癌的进展中起着至关重要的作用,而trans-1-amino-3-[18F]fluorocyclobutanecarboxylic酸(抗[18F]FACBC)被用于前列腺癌的可视化。我们检测了雄激素对与抗[18F]FACBC转运和摄取trans-1-amino-3-fluoro-[1-14C]cyclobutanecarboxylic酸相关的氨基酸转运体(抗[14C]FACBC)表达的影响。研究雄激素受体(AR)阳性的LNCaP和AR阴性的人前列腺癌DU145细胞在5-二氢睾酮(5-α)作用下的氨基酸转运体的表达和抗[14C]FACBC的摄取,以及AR拮抗剂比卡鲁胺对DHT相关改变的影响。DHT可刺激LNCaP细胞氨基酸转运蛋白ASCT2、SNAT5、4F2重链和LAT3的表达,但对DU145细胞无明显影响。抗[14C]FACBC的摄取仅在LNCaP细胞中以DHT依赖的方式增强。DHT增加了ASCT2的表达,ASCT2是负责抗[18F]FACBC摄取的转运体,从而增加了AR阳性LNCaP细胞的抗[14C]FACBC摄取。雄激素介导的诱导可能有助于前列腺癌中独特的抗[18F]FACBC蓄积模式。
Androgens play a crucial role in prostate cancer progression, and trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid (anti-[18F]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.
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