脂质体包裹99^Tc^m-HYNIC-survivinASODN中胞嘧啶含量对荷肝癌裸鼠显像的影响  

Influence of the cytosine content in liposome-coated 99^Tc^m-HYNIC-survivin ASODN on tumor bear- ing nude mice imaging

作　　者：贾红丽[1] 冯珏[2] 张秀梅[2] 方凤宁[2] 杨阳[2] 张自伟[1] 

机构地区：[1]河北医科大学第一医院核医学科,石家庄050081 [2]河北医科大学第二医院核医学科

出　　处：《中华核医学与分子影像杂志》2015年第5期355-358,共4页Chinese Journal of Nuclear Medicine and Molecular Imaging

摘　　要：目的研究胞嘧啶（c）含量对反义探针肿瘤特异性聚集的影响，为最佳反义显像碱基序列的筛选提供帮助。方法以survivin为靶序列制备3种（A1、A2、A3）C含量不同（10％、20％、30％）的20个碱基单链ASODN，耦联HYNIC，经99^Tc^m标记、CellufineGH-25纯化、脂质体包裹后获得3种标记化合物。分别对荷肝癌裸鼠行反义显像，各组计量资料比较采用Kruskal-WallisH检验。结果注射后4h．3种标记化合物在荷肝癌裸鼠体内均表现为肝、肾高摄取。随着C含量升高，3种标记化合物的肾脏摄取依次升高，分别为（1．50±0．06）、（2．80±0．09）和（3．96±0．03）％ID／g；肿瘤摄取依次降低，分别为（2．08±0．08）、（1．69±0．01）和（1．20±0．09）％ID／g；体内显像的rr／NT比值分别为4．49～4．93、4．12～4．21和3．35。3．85，差异有统计学意义（H=12．50，P〈0．05）；生物分布的T／NT比值分别为4．08～4．94、4．02～4．18和3．66-3．85，差异有统计学意义（H=10．82，P〈0．05）。结论SurvivinASODN中的C含量越低，标记化合物的肾内滞留率越低，肿瘤特异性结合率越高，显像质量越好。Objective To investigate whether specific cellular uptake of 99Tcm-survivin-ASODN in nude mice bearing human HCC is influenced by its cytosine content. Methods Three kinds （A1, A2, A3） of synthesized survivin ASODN with three cytosine contents（ 10%, 20%, 30%） , 20 bases per single-strand were prepared. They were labeled with 99Tcm by conjugating with a bifunctional chelator HYNIC, purified through Cellufine GH-25 and then encapsulated with liposome. Antisense gene imaging and the biodistribu- tion of 99Tcm-HYNIC-survivin ASODN in nude mice bearing HCC were performed. The data were analysed by Kruskal-Wallis H test. Results At 4 h post injection, all the 3 labelled compounds showed increased up- take by tumor, liver and kidney. With increase in cytosine content, the uptake increased in kidney （%ID/g ： 1.50±0.06, 2.80±0.09 and 3.96±0.03）, and decreased in tumor （%ID/g： 2.08±0.08, 1.69±0.01 and 1.20±0.09）. T/NT in imaging （4.49-4.93, 4.12-4.21, 3.35-3.85; H= 12.50, P〈0.05） and in biodistri- bution （4.08-4.94, 4.02-4.18, 3.66-3.85 ; H= 10.82, P〈0.05） were all significantly different. Conclu- sion ASODN with lower cytosine content shows higher uptake by HCC tumor cells and less stasis in kid- neys, thus providing better quality in antisense gene imaging.

关 键 词：肝肿瘤 胞嘧啶 寡脱氧核糖核苷酸类 反义 锝 体层摄影术 发射型计算机 单光子 小鼠 裸 

分 类 号：R735.7[医药卫生—肿瘤] R730.44[医药卫生—临床医学]