Transport of free 211At and 125I- in thyroid epithelial cells:: effects of anion channel blocker 4,4′-diisothlocyanostilbene-2,2′-disulfonic acid on apical efflux and cellular retention
Transport of free 211At and 125I- in thyroid epithelial cells:: effects of anion channel blocker 4,4′-diisothlocyanostilbene-2,2′-disulfonic acid on apical efflux and cellular retention
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DOI：
10.1016/j.nucmedbio.2007.03.012
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发表时间：
2007-07-01
影响因子：
3.1
通讯作者：
Nilsson, Mikael
中科院分区：
文献类型：
--
作者：
Lindencrona, Ulrika;Forssell-Aronsson, Eva;Nilsson, Mikael
简介：砹（At-211；a-发射体；t(1/2)-7.21 h）与其卤素邻居碘有一些共同特征。在本研究中，我们研究了4,4'-二异硫氰芪-2,2'-二磺酸（DIDS）是否可用于增加At-211和放射性碘在甲状腺上皮细胞中的细胞保留时间。方法：在双室培养的猪甲状腺细胞中同时研究At-211和I-125(-)的跨上皮转运和细胞摄取。细胞用促甲状腺激素（TSH）或表皮生长因子（EGF）预刺激48小时。此外，还研究了 DIDS 和毛喉素的急性作用。 结果：两种放射性核素的跨上皮转运均受到 TSH 刺激，并被 EGE 下调。在对照和 TSH 刺激的细胞中，DIDS 迅速减少了外流并增加了 I-125(-) 的细胞含量，而 DIDS 对 EGF 处理的细胞中的 I-125(-) 转运没有影响。 DIDS 仅在 TSH 刺激的细胞中阻断 At-211 外流。出乎意料的是，DIDS 导致对照细胞和 EGF 刺激的细胞中 At-211 的加速流出，此外，减少了 EGF 刺激的培养物中 At-211 的细胞含量。 DIDS对毛喉素诱导的两种放射性核素的外排没有影响。结论：甲状腺211 At摄取和外排的幅度与I-125(-)相似，强烈依赖于细胞的功能活性。然而，At-211 外排可能涉及几种对 DIDS 具有不同敏感性的渗透机制，而 I-125(-) 至少部分不具备这些机制。结果表明，阴离子通道阻断可能有助于增加表达 NIS 的肿瘤中 At-211 和放射性碘的吸收剂量。 (c) 2007 Elsevier Inc. 保留所有权利。
Introduction: Astatine (At-211; a-emitter; t(1/2)-7.21 h) shares several features with its halogen neighbour iodine. In the present study, we investigated whether 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) can be used to increase the cellular retention time of At-211 and radioiodide in thyroid epithelial cells.Methods: The transepithelial transport and cellular uptake of At-211 and I-125(-) were studied simultaneously in porcine thyrocytes cultured in bicameral chambers. The cells were prestimulated with thyroid-stirnulating hormone (TSH) or epidermal growth factor (EGF) for 48 h. In addition, the acute effects of DIDS and forskolin were investigated.Results: The transepithelial transport of both radionuclides was stimulated by TSH and down-regulated by EGE DIDS rapidly reduced the efflux and increased the cellular content of I-125(-) in control and TSH-stimulated cells, whereas DIDS had no effect on I-125(-) transport in EGF-treated cells. DIDS blocked the At-211 efflux only in TSH-stimulated cells. Unexpectedly, DIDS caused an accelerated efflux of At-211 in both control and EGF-stimulated cells and, furthermore, reduced the cellular content of At-211 in the EGF-stimutated cultures. DIDS had no effect on the forskolin-induced efflux of the two radionuclides.Conclusions: The magnitude of thyroidal 211 At uptake and efflux is similar to that of I-125(-), strongly dependent on the functional activity of the cells. However, At-211 efflux likely involves several permeating mechanisms with different sensitivity to DIDS, which are at least partly not shared by I-125(-). The results suggest that anion channel blockage is potentially useful to increase the absorbed dose from both At-211 and radioiodine in NIS-expressing tumours. (c) 2007 Elsevier Inc. All rights reserved.