In vitro analysis of transport and metabolism of 4'-thiothymidine in human tumor cells.
In vitro analysis of transport and metabolism of 4'-thiothymidine in human tumor cells.
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DOI：
10.1016/j.nucmedbio.2014.12.005
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发表时间：
2015-05
影响因子：
3.1
通讯作者：
Schwartz JL
中科院分区：
文献类型：
--
作者：
Plotnik DA;Wu S;Linn GR;Yip FCT;Comandante NL;Krohn KA;Toyohara J;Schwartz JL
使用胸苷（TdR）和胸苷类似物（如3′-氟-3 ′-脱氧胸苷（FLT））作为基于正电子发射断层扫描（PET）的增殖标记物可提供肿瘤对治疗反应的信息。对另一种TdR类似物4 '-硫代胸苷（4DST）的研究表明，它可能是比TdR或FLT更好的基于PET的增殖示踪剂。4DST对PET研究中使TdR分析复杂化的催化剂具有抗性，但与FLT不同，4DST被掺入DNA中。为了进一步评价4DST，测定4DST转运和代谢的动力学，并与FLT和TdR进行比较。在指数生长条件下，在人腺癌细胞系A549中检测了FLT、TdR和4DST的转运和代谢。在存在或不存在硝基苄基巯基嘌呤核糖核苷（NBMPR）（平衡核苷转运蛋白（ENT）的抑制剂）的情况下，在补充有放射性标记示踪剂的缓冲液中孵育单细胞悬液。示踪剂吸收的动力学测定在整个细胞和示踪剂代谢测定细胞裂解物的高效液相色谱法。TdR和4DST在ENT依赖性转运、摄取曲线形状和DNA掺入的相对水平方面定性相似。FLT不整合到DNA中，表现出明显的温度效应，其转运具有明显的NBMPR抗性成分。总体而言，4DST代谢明显慢于TdR或FLT。4DST为PET中的TdR提供了良好的替代方案，并且在增殖测量中优于FLT。然而，缓慢的4DST代谢和11 C标记的短半衰期可能限制PET的广泛使用。
The use of thymidine (TdR) and thymidine analogs such as 3′-fluoro-3′-deoxythymidine (FLT) as positron emission tomography (PET)-based proliferation markers can provide information on tumor response to treatment. Studies on another TdR analog, 4'-thiothymidine (4DST), suggest that it might be a better PET-based proliferation tracer than either TdR or FLT. 4DST is resistant to the catabolism that complicates analysis of TdR in PET studies, but unlike FLT, 4DST is incorporated into DNA. To further evaluate 4DST, the kinetics of 4DST transport and metabolism were determined and compared to FLT and TdR. Transport and metabolism of FLT, TdR and 4DST were examined in the human adenocarcinoma cell line A549 under exponential-growth conditions. Single cell suspensions were incubated in buffer supplemented with radiolabeled tracer in the presence or absence of nitrobenzylmercaptopurine ribonucleoside (NBMPR), an inhibitor of equilibrative nucleoside transporters (ENT). Kinetics of tracer uptake was determined in whole cells and tracer metabolism measured by high performance liquid chromatography of cell lysates. TdR and 4DST were qualitatively similar in terms of ENT-dependent transport, shapes of uptake curves, and relative levels of DNA incorporation. FLT did not incorporate into DNA, showed a significant temperature effect for uptake, and its transport had a significant NBMPR-resistant component. Overall 4DST metabolism was significantly slower than either TdR or FLT. 4DST provides a good alternative for TdR in PET and has advantages over FLT in proliferation measurement. However, slow 4DST metabolism and the short half-life of the 11C label might limit widespread use in PET.
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DOI：
10.1152/ajpcell.2001.281.6.c1991
发表时间：
2001-12-01
影响因子：
5.5
作者：
Szkotak, AJ;Ng, AML;Duszyk, M
通讯作者：
Duszyk, M
影响因子：
4.8
作者：
Ward, JL;Sherali, A;Tse, CM
通讯作者：
Tse, CM
影响因子：
8.8
作者：
Hubeek, I;Stam, RW;Kaspers, GJL
通讯作者：
Kaspers, GJL
影响因子：
3.1
作者：
Grierson, JR;Schwartz, JL;Krohn, KA
通讯作者：
Krohn, KA
影响因子：
3.1
作者：
Plotnik, David A.;McLaughlin, Lena J.;Schwartz, Jeffrey L.
通讯作者：
Schwartz, Jeffrey L.