Imaging of radioiodine-labeled KH901, a tumor-specific oncolytic recombinant adenovirus, in nude mice with human hepatocellular carcinoma
Imaging of radioiodine-labeled KH901, a tumor-specific oncolytic recombinant adenovirus, in nude mice with human hepatocellular carcinoma
复制标题
放射性碘标记的 KH901（一种肿瘤特异性溶瘤重组腺病毒）在患有人肝细胞癌的裸鼠中的成像
DOI：
10.1097/mnm.0b013e3283371410
复制
发表时间：
2010-05-01
影响因子：
1.5
通讯作者：
Long, Ya-Hong
中科院分区：
文献类型：
--
作者：
Mi, Yan-Xia;Li, Yun-Chun;Long, Ya-Hong
目的研究肿瘤特异性溶瘤腺病毒125I/131I标记的重组腺病毒KH901在荷人肝癌裸鼠体内的分布和显像。方法采用N-溴代丁二酰亚胺标记法对KH901进行125I/131I标记。采用酶联免疫吸附试验检测粒细胞-巨噬细胞集落刺激因子活性。瘤内注射125I-KH901后，在荷瘤裸鼠的不同器官和肿瘤组织中跟踪标记。将131I-KH901直接注射到荷瘤裸鼠体内，在放射性核素图像上检测不同时间的药物浓度。结果125I/131I-KH901放化纯度大于95%。131I-KH901刺激肿瘤细胞大量表达粒-巨噬细胞集落刺激因子。加入131I-KH90124小时后，肿瘤细胞和正常细胞中粒细胞-巨噬细胞集落刺激因子的浓度分别为183.27±6.9和20.44±0.77 pg/ml。~(131)I-KH901主要分布于肿瘤内，滞留时间较长，24 h时为14.93%ID/g，放射性核素显像显示~(131)I-KH901在肿瘤内滞留显著。注射后2 h全身扫描肿瘤显示清晰。结论125I或131I-KH901可特异性地在肿瘤部位聚集，是一种肿瘤溶瘤腺病毒和放射性核素联合治疗癌症的新药。
ObjectiveTo study the biodistribution and imaging of 125I/131I-labeled KH901, a tumor-specific oncolytic recombinant adenovirus, in nude mice bearing human hepatocarcinoma. MethodsKH901 was labeled with 125I/131I according to the N-bromosuccinimide labeling method. The activity of granulocyte-macrophage colony-stimulating factor was determined by enzyme-linked immunosorbent assay. After 125I-KH901 was injected into the tumor, the label was followed in different organs and tumor tissues in nude mice with hepatocellular carcinoma. 131I-KH901 was injected directly into the tumor of nude mice bearing hepatocellular carcinoma, and their concentrations were detected at different times on radionuclide images. ResultsThe radiochemical purity of 125I/131I-KH901 was over 95%. 131I-KH901 stimulated massive expression of granulocyte-macrophage colony-stimulating factor in tumor cells. Twenty-four hours after the addition of 131I-KH901, the concentrations of granulocyte-macrophage colony-stimulating factor were 183.27±6.90 and 20.44±0.77 pg/ml in tumor and normal cells, respectively. 125I-KH901 was mainly distributed in the tumor and had a longer retention time, which was 14.93%ID/g at 24 h. Radionuclide imaging showed that the radioactive retention of 131I-KH901 in the tumor was significant. The tumor was shown clearly in the whole-body scan at 2 h after injection. Conclusion125I or 131I-KH901 concentrates specifically at the tumor site, which makes it a novel drug (combination of oncolytic adenovirus and radionuclide therapies) for the treatment of cancer.