Imaging paclitaxel (chemotherapy)-induced tumor apoptosis with 99mTc C2A, a domain of synaptotagmin I:: a preliminary study
Imaging paclitaxel (chemotherapy)-induced tumor apoptosis with 99mTc C2A, a domain of synaptotagmin I:: a preliminary study
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DOI：
10.1016/j.nucmedbio.2007.12.007
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发表时间：
2008-04-01
影响因子：
3.1
通讯作者：
Zheng, Yuming
中科院分区：
文献类型：
--
作者：
Wang, Feng;Fang, Wei;Zheng, Yuming
目的：为了评估在小鼠模型中使用Tc-99 m标记的突触结合蛋白I的C2 A结构域对紫杉醇治疗诱导的非小细胞肺癌（NSCLC）细胞凋亡进行成像的动力学和可行性，材料和方法：给荷瘤小鼠静脉注射紫杉醇，12、24、48和72 h后静脉注射Tc-99 m-C2 A-GST，并在注射后2、4和6小时在装有针孔准直器的双头γ照相机上获得平面图像。通过ROT分析计算肿瘤与正常组织的比值（T/NT），并反映Tc-99 m-C2 A-GST的特异性结合。6 h后处死小鼠，流式细胞术检测caspase-3作为凋亡执行者的作用，TUNEL法检测DNA片段化。而使用灭活的C2 A-GST估计非特异性蓄积。结果：紫杉醇诱导后T/NT显著增加，而未治疗组T/NT较低（T/NT=1.24 ± 0.23）。就% ID/g而言，处理后第2组（12 h）、第3组（24 h）、第4组（48 h）和第5组（72 h）的活性分别为2.05 +/- 0.20、3.02 +/- 1.01、3.17 +/- 1.16和3.96 +/- 1.72。而在未治疗组中，第I组% ID/g为1.21 +/- 0.51。放射性示踪剂摄取与凋亡指数呈正相关（r = 0.70，P
Purpose: To evaluate the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using Tc-99m-labeled C2A domain of synaptotagmin I in a mouse model,Materials and Methods: H460 tumor-bearing mice were treated with intravenous paclitaxel, and 12, 24, 48 and 72 h later, Tc-99m-C2A-GST was injected intravenously, and planar images were acquired at 2, 4 and 6 h postinjection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROT analysis and reflected specific binding of Tc-99m-C2A-GST. Mice were sacrificed after 6-h imaging; caspase-3 as apoptosis executer was determined by flow cytometry; DNA fragmentation was analyzed by terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Whereas nonspecific accumulation was estimated using inactivated C2A-GST. The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity.Results: T/NT significantly increased after paclitaxel inducement, whereas it was low in untreated tumors (T/NT=1.24 +/- 0.23). In terms of % ID/g, activity in Group 2 (12 h), Group 3 (24 h), Group 4 (48 h) and Group 5 (72 h) after the treatment was 2.05 +/- 0.20, 3.02 +/- 1.01, 3.17 +/- 1.16 and 3.96 +/- 1.72, respectively. Whereas in the nontreated group, Group I % ID/g was 1.21 +/- 0.51. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.70, P