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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 study the value of 99mTc labeled survivin antisense oligonucleotide (ASON) imaging in the diagnosis of hepatocellular carcinoma. Methods The single strand survivin ASON was synthesized by DNA synthesizer. The survivin ASON was labeled with S acetyl N - hydroxysuccinimide (SacetylNHSMAG3) as a chelator at the 5 ’ The biological distribution of 99mTcsurvivin ASON in tumor-bearing (SMMC7721) nude mice model, tumor antisense gene imaging and tumor antisense gene suppressive imaging were analyzed. Results Tumor tissue imaging time as early as 0.5h has begun to develop. The aggregation of 99mTcsurvivin ASON in tumor tissue increased gradually with time and reached the maximum at 4h. The tumor / contralateral limb muscle ratios were 2.48 ± 0.44 (in vitro imaging) and 3.35 ± 0.57 (biological distribution), respectively. The concentration of sense oligonucleotide (SON) in tumor tissue at each time point was significantly lower than that of ASON, the difference was statistically significant (P <0.01). 99mTcsurvivin ASON decreased significantly in tumor tissue after uninhibited survivin ASON inhibition. The ratio of tumor to contralateral muscle at 4h was 0.93 ± 0.23, which was significantly lower than that before inhibition (2.48 ± 0.44, P < 0.01). Conclusion 99mTcsurvivin ASON can specifically accumulate in the tumor tissue of nude mice bearing tumor model, providing a new possible method for the specific diagnosis of hepatocellular carcinoma.