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.
出处
《中华核医学与分子影像杂志》
北大核心
2015年第5期355-358,共4页
Chinese Journal of Nuclear Medicine and Molecular 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
Liver neoplasms
Cytosine
Oligodeoxyribonueleotides, antisense
Technetium
Tomography, emission-computed, single-photon
Mice, nude