脂质体介导的^(99)Tc^m-反义寡聚核苷酸在荷瘤裸鼠体内分布及显像研究  

Study on biodistribution and imaging of liposome-mediated ^(99)Tc^m labeled antisense oligonucleotides of mRNA of c-myc in tumor-bearing nude mice

作　　者：郑建国[1] 谭天秩[1] 匡安仁[1] 李云春[1] 张春[1] 潘卫民[1] 

机构地区：[1]华西医科大学附属第一医院核医学科,成都610041

出　　处：《中华核医学杂志》2001年第6期349-350,I003,共3页Chinese Journal of Nuclear Medicine

基　　金：国家自然科学基金资助项目 (3980 2 0 0 )

摘　　要：目的　研究脂质体介导的99Tcm 反义寡聚核苷酸在荷瘤裸鼠体内的分布及反义显像诊断结肠癌的可能性 ,为反义显像和反义治疗的临床应用提供实验依据。方法　制作荷瘤裸鼠模型 ,每只小鼠尾静脉注射约 0 .30MBq脂质体包裹的99Tcm 反义寡聚核苷酸 ,于不同时间眼眶静脉采血后处死小鼠 ,测定不同组织中及标准源的放射性计数。荷瘤裸鼠尾静脉注入脂质体介导的99Tcm 反义寡聚核苷酸 (30～ 90mg) ,于注射后不同时间显像 ,观察其在肿瘤组织的浓聚情况 ,并以脂质体介导的99Tcm 标记的正义和无义寡聚核苷酸为对照。结果　胃、网状内皮系统和肿瘤组织放射性浓聚较高 ,其次为心和血 ,余组织中放射性分布较少。肿瘤组织中放射性在 2h时达到高峰 ,以后迅速降低。在 2h时 ,脂质体介导的99Tcm 反义寡聚核苷酸能清晰显示肿瘤部位 ,而对照组则不能。结论　脂质体介导的99Tcm 反义寡聚核苷酸可用于结肠癌的诊断 ,但临床应用前还需进行大量的研究。Objective To investigate the biodistribution of liposome-mediated 99Tcm-antisense oligonucleotides of mRNA of c-myc (DNA), the possibility by using it to diagnose colorectal cancer, and to provide experimental basis for the clinical application of antisense 99Tcm-DNA imaging and treatment. Methods The tumor-bearing nude mice were constructed in advance. ①Twenty tumor bearing mice were given liposome-mediated 99Tcm-DNA intravenously at a dose of 0.30 MBq/mouse. After the blood samples being obtained through orbital vein at different intervals, the mice were sacrificed by cervical dislocation, and tissue samples were studied. ②Liposome-mediated 99Tcm-DNA then was injected to 20 tumor-bearing mice at a dose of 37 MBq/mouse. The mice were scanned at 1, 1.5, 2, 4, 6 and 24 h with SPECT to observe the accumulation of the tracer in the tumor. Meanwhile liposome-mediated 99Tcm labeled sense and scrambled oligonucleotides serving as controls. Results The stomach, reticuloendothelial system and tumor tissue played an important role in biodistribution; heart and blood were the next; and radioactivity counts in other tissues were low. The radioactivity in cancer reached its peak at 2 h after injection, and then decreased rapidly. At the peak time of accumulation the tumor could be viewed clearly. However the tumor couldn't be found in control groups. Conclusions Liposome-mediated 99Tcm-DNA could be used for diagnosing colorectal cancer. Nevertheless great deal of research work needed to be done before clinical application.

关 键 词：反义寡核苷酸类 脂质体 放射性核素显像 结肠癌 诊断 

分 类 号：R817.1[医药卫生—影像医学与核医学]