^(99m)Tc标寡核苷酸用于家兔粥样斑块分子显像研究  

Technetium-99m labeled oligonucleotides-an molecular imaging of atherosclerotic plaques in a rabbit model

作　　者：秦光明[1] 张永学[2] 安锐[2] 高再荣[2] 曹卫[2] Donald J.Hnatowich 

机构地区：[1]深圳市第二人民医院核医学科,深圳518035 [2]华中科技大学协和医院核医学科 [3]Division of Nuclear Medicine,Depart ment of Radiology,University of Massachusetts Medical School

出　　处：《临床心血管病杂志》2008年第7期526-529,共4页Journal of Clinical Cardiology

基　　金：国家自然科学基金资助项目(No:30070310)

摘　　要：目的:建立锝-99m(99mTc)标记寡核苷酸的方法,并用于家兔动脉粥样硬化斑块分子显像。方法:以高胆固醇饲料喂饲新西兰大耳白兔约2个月,复制成动脉粥样硬化家兔模型。寡核苷酸进行99mTc标记后注入家兔,进行生物学分布以及体内、体外显像研究。结果:寡核苷酸99mTc标记率为(77.8±6.8)%(n=7)。生物学分布实验表明,与SON相比,c-mycASON在粥样斑块中的浓聚程度明显要高。c-mycASON体内显像可见腹主动脉部位散在性显像剂浓聚,体外主动脉显像提示放射性浓聚灶与斑块所在部位吻合。未偶联组未见阳性显像结果。结论:99mTc标记反义寡核苷酸有望成为一种新的显像剂,在分子水平上用于动脉粥样硬化的早期、特异和无创性的诊断。Objective：The proto-oncogenes activation results in an increased expession of their mRNAs in the cytosol during atherosclerotic process. With radiolabeled antisense oligonucleotides, the mRNA overexpression might be traced, which resulted in visible atherosclerotic plaques. Method：The oligonucleotides were radiolabeled with 99m-Technetium through the bifunctional chelator NHS-MAG3. Atherosclerosis was induced in New Zealand White rabbits fed with 1% cholesterol for approximately 60 days. Biodistribution studies were performed after 37MBq of ^99mTc labeled c-myc mRNA ASON or SON was injected. The rabbits were killed at different timepoints postinjection and tissues were harvested, weighed and counted on a γ counter. The percent uptake per gram tissue, plaque to blood and plaque to myocardium ratios were calculated. In vivo and ex vivo imaging were performed in hyperlipidemic rabbits and control rabbits after i. v. injection of （92.5± 18.5） MBq ^99mTc-ASON or SON. Immediately after the molecular imaging, the animals were killed, and ex vivo imaging of the aortic specimens was performed. Result：The MAG3-DNA was labeled with ^99mTc at room temperature and neutral pH, with a mean labeling efficiency of （77.8 ± 6.8）% （n = 7）. Rabbit biodistribution studies revealed highest accumulation in the kidneys. The tracer accumulation in the atherosclerotic plaque was higher in case of c-myc ASON, as compared to SON. Planar imaging revealed scattered accumulation of ^99mTc labeled c-myc ASON along the artery wall. Ex vivo imaging further demonstrated that the activity-accumulation area matched the area of plaques as observed after the rabbits were killed. In cases of the control group, no positive results were achieved in either in vivo or ex vivo studies. Conclusion：This molecular imaging approach may provide a new sensitive tool for noninvasive imaging of atherosclerotic plaques at an earlier stage.

关 键 词：动脉粥样硬化 分子显像 反义寡聚核苷酸 ^99M锝 

分 类 号：R544.2[医药卫生—心血管疾病]