Kinetic analyses of trans-1-amino-3[18F]fluorocyclobutanecarboxylic acid transport in Xenopus laevis oocytes expressing human ASCT2 and SNAT2
Kinetic analyses of trans-1-amino-3[18F]fluorocyclobutanecarboxylic acid transport in Xenopus laevis oocytes expressing human ASCT2 and SNAT2
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DOI：
10.1016/j.nucmedbio.2013.03.009
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发表时间：
2013-07-01
影响因子：
3.1
通讯作者：
Kawai, Keiichi
中科院分区：
文献类型：
--
作者：
Okudaira, Hiroyuki;Nakanishi, Takeo;Kawai, Keiichi
简介：反式-1-氨基-3-[F-18]氟环丁烷羧酸（anti-[F-18] FACBC）是一种很有前途的氨基酸正电子发射断层扫描（PET）放射性示踪剂，可用于前列腺癌的显像。我们先前表明，抗FACBC是由氨基酸转运蛋白，特别是丙氨酸-丝氨酸-半胱氨酸转运蛋白2（ASCT2），这是与肿瘤生长。我们研究了这种亲和力，以评估抗FACBC运输在前列腺癌cells. Methods的机制：动力学测定反式-1-氨基-3-氟-[1-C-14]环丁烷羧酸（[C-14] FACBC）进行非洲爪蟾卵母细胞过表达ASCT2或钠偶联中性氨基酸转运蛋白2（SNAT 2），这两个是高度表达的前列腺癌细胞。我们还使用过表达系统L氨基酸转运蛋白1或2（LAT1或LAT2）的哺乳动物细胞系检测了[C-14] FACBC摄取的动力学。结果：ASCT2和SNAT 2转运[C-14] FACBC的米氏动力学Km值分别为92.0 +/-32.3 μ M和222.0 +/-293 μ M。LAT1和LAT2转运[C-14] FACBC，Michaelis-Menten K-m值分别为230.4 +/-184.5 μ M和738.5 +/-87.6 μ M。抗FACBC对ASCT2的亲和力高于对SNAT 2、LAT 1或LAT 2的亲和力。抗[F-18] FACBC在癌细胞中的ASCT2优先转运可用于更有效的前列腺癌成像。(C)2013 Elsevier Inc. All rights reserved.
Introduction: Trans-1-amino-3[F-18]fluorocyclobutanecarboxylic acid (anti-[F-18]FACBC) is a promising amino acid positron emission tomography (PET) radiotracer for visualizing prostate cancer. We previously showed that anti-FACBC is transported by amino acid transporters, especially by alanine-serine-cysteine transporter 2 (ASCT2), which is associated with tumor growth. We studied this affinity to assess the mechanism of anti-FACBC transport in prostate cancer cells.Methods: Kinetic assays for trans-1-amino-3-fluoro-[1-C-14]cyclobutanecarboxylic acid ([C-14]FACBC) were performed in Xenopus laevis oocytes over-expressing either ASCT2 or sodium-coupled neutral amino acid transporter 2 (SNAT2), both of which are highly expressed in prostate cancer cells. We also examined the kinetics of [C-14]FACBC uptake using mammalian cell lines over-expressing system L amino acid transporter 1 or 2 (LAT1 or LAT2).Results: ASCT2 and SNAT2 transported [C-14]FACBC with Michaelis-Menten kinetics K-m values of 92.0 +/- 32.3 mu M and 222.0 +/- 293 mu M, respectively. LAT1 and LAT2 transported [C-14]FACBC with Michaelis-Menten K-m values of 230.4 +/- 184.5 mu M and 738.5 +/- 87.6 mu M, respectively.Conclusions: Both ASCT2 and SNAT2 recognize anti-FACBC as a substrate. Anti-FACBC has higher affinity for ASCT2 than for SNAT2, LAT1, or LAT2. The ASCT2-preferential transport of anti-[F-18]FACBC in cancer cells could be used for more effective prostate cancer imaging. (C) 2013 Elsevier Inc. All rights reserved.