放射性药物^(99m)Tc-HL91在大鼠脑缺血模型的初步研究  

Use of hypoxia imaging agent99mTcHL91 in rat cerebral ischemia models

作　　者：周颖[1,2,3] 屈婉莹[1,2,3] 李萌[1,2,3] 陈方[1,2,3] 姚稚明[1,2,3] 朱明[1,2,3] 朱霖[1,2,3] 

机构地区：[1]北京医院核医学科 [2]北京协和医院核医学科 [3]国家标准物质研究中心

出　　处：《中华放射医学与防护杂志》1999年第4期275-278,共4页Chinese Journal of Radiological Medicine and Protection

基　　金：国家攀登计划B项目资助

摘　　要：目的探讨国内首次合成的放射性药物９９ｍＴｃＨＬ９１在脑血管疾病诊断中应用的可能性。方法对９９ｍＴｃＨＬ９１进行一般性质、标记率、体外稳定性、异常毒性和正常小鼠体内生物分布等实验。建立１５只大鼠脑缺血模型，并在该模型上进行９９ｍＴｃＨＬ９１体内分布和乏氧显像研究。结果①ＨＬ９１药盒标记简便，安全稳定。②正常小鼠静脉注射９９ｍＴｃＨＬ９１后血中放射性迅速下降，肝、肾和胃肠道的放射性较高，心肺清除很快，正常脑组织摄取低。③处死前脑部显像及处死后离体脑组织显像均于注射９９ｍＴｃＨＬ９１４小时后可见患侧脑组织较对侧放射性增高，且显示的缺血区范围大致相似。④在不同时相离体脑组织显像图上，利用感兴趣区技术，计算患／健侧大脑中动脉供血区脑组织放射性比值分别为０９８±００６、０９９±００５、１２９±００３、１５６±０１４、１６６±００６，除１与２、８与１２小时外，其余各组间两两比较差异均有显著性（Ｐ＜００５～Ｐ＜０００１）。⑤体外测量缺血侧脑组织与正常脑组织单位重量放射性比值随注射放射性药物的时间延长而逐渐增高。结论９９ｍＴｃＨＬ９１在缺血缺氧脑组织滞留增加，清除速度减缓。实验研究和临床应?Objective\ To explore the possibility of diagnosis for cerebrovascular disease by a novel synthetic hypoxia agent99mTcHL91 used in rat cerebral ischemia models. Methods Pharmacological experiments of 99mTcHL91 were carried out including common properties, radiochemical purity, stability in vitro, anomalous toxicity test and biodistribution in mice. Fifteen cerebral ischemic rat models were established and received 99mTcHL91 scintigraphy. Results HL91 kits were labeled with 99mTc easily and showed high radiochemical purity and stability.Rapid clearance in blood, heart and lungs and high activity in liver, kidneys and intestines were observed. Relatively low uptake in brain was identified. The radioactivity in ischemic brain tissue increased significantly at 4h postinjection in both rat images and isolated brain images.The radioactivity ratios of lesion to normal brain tissue by drawing ROIs in isolated brain planar images were 098006,099005,129003,156014 and 166006 at 1,2,4,8 and 12 h postinjection, respectively. There were significant differences among all groups except for 1 h and 2 h, 8 h and 12 h postinjection (P<005P<0001). The radioactivity ratios in per unit weight of ischemic to normal brain tissues were gradually increasing. Conclusion Increased retention ratio and decreased clearance rate of 99mTcHL91 in the hypoxic, ischemic brain tissue have been proved. It is appropriate to perform imaging at 4 h postinjection.

关 键 词：锝99M HL91 大鼠 脑缺血 动物模型 

分 类 号：R743.33[医药卫生—神经病学与精神病学]