Correlation of 4′-[methyl-11C]-thiothymidine uptake with human equilibrative nucleoside transporter-1 and thymidine kinase-1 expressions in patients with newly diagnosed gliomas

Correlation of 4′-[methyl-11C]-thiothymidine uptake with human equilibrative nucleoside transporter-1 and thymidine kinase-1 expressions in patients with newly diagnosed gliomas
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新诊断胶质瘤患者4′-[甲基-11C]-硫代胸苷摄取与人平衡核苷转运蛋白-1和胸苷激酶-1表达的相关性

DOI:
10.1007/s12149-018-1285-5
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发表时间:
2018
影响因子:
2.6
通讯作者:
Nishiyama Yoshihiro
Nishiyama Yoshihiro
中科院分区:
医学4区
文献类型:
--
作者:
Takami Yasukage;Yamamoto Yuka;Ueno Masaki;Chiba Yoichi;Norikane Takashi;Hatakeyama Tetsuhiro;Miyake Keisuke;Toyohara Jun;Nishiyama Yoshihiro

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目的检测人平衡核苷转运蛋白-1(hENT1)和4'-[甲基-11C]-硫胸苷(4DST)磷酸化关键酶胸苷激酶-1(TK1)的表达,阐明初诊胶质瘤患者摄取4DST的机制。方法 共19例初诊胶质瘤患者 使用 4DST PET 检查神经胶质瘤。肿瘤病变被确定为局部摄取增加的区域,超过正常大脑背景的摄取。对于半定量分析,肿瘤与对侧正常脑组织 (T/N) 的比率通过将肿瘤的最大标准化摄取值 (SUV) 除以参考组织的平均 SUV 的值来确定。采用免疫组化法检测肿瘤标本中hENT1、TK1和Ki-67的表达,并与4DST T/N比值进行比较。结果除两例外,所有胶质瘤均显示4DST摄取局灶性增加。除一例 II 级神经胶质瘤外,所有神经胶质瘤均显示 hENT1 染色,该神经胶质瘤在 4DST PET 上也未显示。 T/N 比值与 hENT1 评分之间存在显着相关性(ρ= 0.90,p< 0.001)。所有神经胶质瘤均显示 TK1 染色,但两个神经胶质瘤除外,这两个神经胶质瘤在 4DST PET 上也未显示。 T/N比值与TK1评分之间存在显着相关性(ρ= 0.92,p< 0.001)。 T/N比值与Ki-67指数之间存在显着相关性(ρ= 0.50,p< 0.03)。结论本初步研究结果表明hENT1和TK1的表达似乎是新诊断胶质瘤中4DST摄取的重要决定因素。
ObjectiveWe examined expressions of human equilibrative nucleoside transporter-1 (hENT1) and thymidine kinase-1 (TK1), the key enzyme in 4′-[methyl-11C]-thiothymidine (4DST) phosphorylation, to elucidate the mechanism of 4DST uptake in patients with newly diagnosed gliomas.MethodsA total of 19 patients with newly diagnosed gliomas were examined with 4DST PET. Tumor lesions were identified as areas of focally increased uptake, exceeding that of normal brain background. For semi-quantitative analysis, tumor-to-contralateral normal brain tissue (T/N) ratio was determined by dividing the maximal standardized uptake value (SUV) for tumor by that of the mean SUV for reference tissue. The expressions of hENT1, TK1 and Ki-67 in tumor specimens were examined by immunohistochemistry and compared with 4DST T/N ratio.ResultsAll but two gliomas showed focally increased 4DST uptake. All gliomas showed hENT1 staining, except one grade II glioma, which was also not visualized on 4DST PET. A significant correlation was observed between T/N ratio and hENT1 score (ρ= 0.90,p< 0.001). All gliomas showed TK1 staining, except two gliomas which were also not visualized on 4DST PET. There was a significant correlation between T/N ratio and TK1 score (ρ= 0.92,p< 0.001). There was a significant correlation between T/N ratio and Ki-67 index (ρ= 0.50,p< 0.03).ConclusionResults of this preliminary study indicate that expressions of hENT1 and TK1 appear to be important determinants of 4DST uptake in newly diagnosed gliomas.
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DOI: --
发表时间: 2014
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