锝-99m标记survivin反义寡核苷酸肝细胞癌显像的实验研究  

Use of ^(99m)Tc-survivin antisense oligonucleotide in diagnosis of hepatocellular carcinoma: an experiment with mice

作　　者：高再荣[1] 张永学[1] 张凯军[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院核医学科,武汉430022

出　　处：《中华医学杂志》2005年第33期2327-2330,共4页National Medical Journal of China

基　　金：湖北省自然科学基金资助项目(2002AB121)

摘　　要：目的研究放射性核素锝99m(99mTc)标记survivin反义寡核苷酸(ASON)显像诊断肝细胞癌的价值。方法用DNA合成仪合成18碱基单链survivinASON,在5′末端经氨基修饰后,以S乙酰基N羟基琥珀酰亚胺巯基乙酰基三甘氨酸(SacetylNHSMAG3)作为螯合剂对survivinASON进行99mTc标记,并对99mTcsurvivinASON在荷瘤(SMMC7721)裸鼠模型体内的生物学分布、肿瘤反义基因显像、肿瘤反义基因抑制显像进行了分析。结果肿瘤组织显像时间早,0.5h即已开始显影。99mTcsurvivinASON在肿瘤组织内的聚集程度随时间延长而逐渐增加,于4h时达到最大,肿瘤/对侧肢体肌肉比值分别为2.48±0.44(体外显像)和3.35±0.57(生物学分布)。正义寡核苷酸(SON)在肿瘤组织内的聚集各时间点均明显低于ASON,差异有统计学意义(P<0.01)。用未标记的survivinASON进行抑制后,99mTcsurvivinASON在肿瘤组织中的聚集明显减少,4h时的肿瘤/对侧肢体肌肉比值降为0.93±0.23,与抑制前的2.48±0.44相比有明显减低(P<0.01)。结论99mTcsurvivinASON可在荷瘤裸鼠模型的肿瘤组织中特异性聚集,为肝细胞癌的特异性诊断提供了一种可能的新方法。Objective To investigate the possibility of using survivin antisense oligonucleotide （ASON） labeled with radionuclide technetium-99m （^99mTc） for diagnosing hepatocellular carcinoma in nude mice bearing human bepatoma- Methods A 18 mer single-stranded survivin ASON sequence was synthesized and linked with a primary amine on the 5＇-end. Survivin ASON was labeled with ^99mTc by conjugating the chelator, S-acetyl-NHS-MAG3 （mercaptoacetyltriglycine）. The biedistribution, antisense gene imaging and antisense gene inhibition imaging of ^99mTc-survivin ASON in nude mice bearing human hepatocellular carcinoma （SMMC-7721） were studied. Results Tumor lesion was early detected with ^99mTc-survivin ASON and the lesion image showed up at 0.5 h postinjection. The accumulation of ^99mTc- survivin ASON in tumor tissue gradually increased and reached the top at 4 h postinjection. The % ID/g （percentage of injected dose per gram of tissue） of ^99mTc-survivin ASON in tumor tissue at 4 h postinjection was 0. 69% ±0. 11%. And the ratios of tumor to muscle were 3.35 ± 0. 57 in biodistribution study and 2. 48：1：0. 44 in antisense imaging study. But the % ID/g of ^99mTc-survivin SON （ sense oligonucleotide） in tumor tissue was only 0. 17% ± 0. 01% at 4 h postinjection. And the ratios of tumor to muscle were 0. 74 ± 0. 04 in biodistribution study and 1.15 ± 0. 36 in antisense imaging study. Both results of % ID/g of tumor tissue and ratio of tumor to muscle in SON group were significantly lower than those in ASON group at every check-time （ P 〈 0. 01 ）. Furthermore, the tumor imaging was diminished in nude mice pretreateted with unlabeled survivin ASON, and the ratio of tumor to muscle was only 0.93 ± 0. 23 at 4 h postinjection and significantly lower than 2. 48 ± 0. 44 in nude mice untreated （P 〈 0. 01 ）. Conclusion The accumulation of ^99mTc-survivin ASON in hepatocellular carcinoma tissue is specific. The antisense imaging with ^99mTc- survivin ASON may be a promising method for diagnos

关 键 词：寡核苷酸类 反义 癌 肝细胞 放射性核素显像 SURVIVIN反义寡核苷酸 锝-99m 显像诊断 肝细胞癌 ^99MTC标记 实验研 N-羟基琥珀酰亚胺 

分 类 号：R735.7[医药卫生—肿瘤] R817.4[医药卫生—临床医学]