特异性溶瘤重组腺病毒KH901的碘标记方法及其生物学分布

Iodination Conditions of KH901,a Tumor-specific Oncolytic Recombinant Adenovirus,and Its ^(125)I-labeled Compounds Biodistribution in Animals

研究一种125I直接标记特异性溶瘤重组腺病毒KH901的简便高效的方法,以及评价125I-KH901的体内生物学行为。采用N-溴代琥珀酰亚胺(NBS)方法对KH901进行标记,确定最佳标记条件;用凝胶过滤层析法对标记物进行分离纯化,纸层析法测定放化纯度。对125I-KH901进行正常小鼠体内生物学分布检测。结果显示,125I-KH901的放化纯达到95%以上,标记率可达到78%;正常小鼠尾静脉注射125I-KH901后体内分布显示肝脏中放射性浓集度最高,24h检测肝脏仍有较多放射性滞留,可达13.34%ID/g,标记物在肾脏的摄取也较高,为8.06%ID/g。因此,N-溴代琥珀酰亚胺(NBS)方法是一种步骤简便、标记率高的比较理想的碘标记病毒方法,125I-KH901主要分布在肝脏和肾脏。

In this research was developed high efficiency method using ^125I for directly labeling KH901, a tumorspecific oncolytic recombinant adenovirus, biodistribution of ^125I-labeled compound in normal mice was investigated. ^125I-KHg01 was prepared by N-bromosuecinimide labeling method to find the optimal ratio of labeling response. The compounds were isolated and purified by Sephadex-G10 agarose and the radiochemical purity of compounds was analyzed by paper chromatography. The radioactivity biodistribution in mice was measured at different times after caudal vein injection with 0. 1 ml ^125I-KH901. The labeling yield of ^125I-KH901 was 78% and the radiochemical purity was 95% after purification by Sephadex-G10 agarose. Biodistribution revealed that the uptake of ^125I-KH901 in liver was higher than in other organs at all time points of the experiment. ^125I-KH901 was mainly concentrated in liver, kidneys, spleen and lung. It can be seen that N-bromosuccinimide labeling method is an optimal method with simple steps and high labeling yield in labeling KH901 with ^125I. ^125I-KH901 has a biodistribution trait which is an advantage to treating liver tumors.