心肌显像剂^(99m)TcN(NOEt)_2的临床前药理研究  

Preclinical pharmacological study of a neutral myocardial imaging agent 99m Tc NOEt

作　　者：方平[1,2] 万卫星[1,2] 吴春英[1,2] 周翔[1,2] 陈正平[1,2] 纪书仁[1,2] 

机构地区：[1]无锡核医学国家重点实验室 [2]江苏省原子医学研究所

出　　处：《中华核医学杂志》1997年第4期230-232,共3页Chinese Journal of Nuclear Medicine

基　　金：江苏省自然科学基金;卫生部优秀青年人才专项科研基金

摘　　要：对心肌显像剂９９ｍＴｃＮ（ＮＯＥｔ）２（ＮＯＥｔ：Ｎ乙氧基，Ｎ乙基氨荒酸钠盐）进行了临床前药理研究，主要包括兔血药清除动力学，大鼠体内分布，狗显像及毒性等。制备的９９ｍＴｃＮ（ＮＯＥｔ）２放化纯度大于９０％，室温放置６小时稳定。分布半衰期＝２５３分钟，消除半衰期＝３３０分钟，清除率＝３７８ｍｌ／ｈ。药物能很快被大鼠心肌摄取并保留，５、３０、６０和９０分钟时分别为４６９、４２０、３９５和３４３％ＩＤ／ｇ，６０分钟时心／肺比值为１１６。狗显像显示９９ｍＴｃＮ（ＮＯＥｔ）２从肺中清除比心肌快，１０、３０和６０分钟时的心／肺比值分别为１６９、２４０和２５５，３０分钟心肌显像清晰，９０分钟全身显像显示心肌摄取为２８２％ＩＤ，但肝脏摄取高达３０１３％ＩＤ。小鼠对药物的耐受量为人的６１４倍。研究表明，９９ｍＴｃＮ（ＮＯＥｔ）２具有临床研究价值。PURPOSE To explore the biological properties of the neutral myocardial imaging agent 99m Tc NOEt. METHODS We prepared this complex and investigated the preclinical pharmacology in animals. Kinetics of blood clearance in rabbits, biodistribution in rats and myocardial imaging in dogs were studied. RESULTS Radiochemical purity of 99m Tc NOEt was over 90% and stable for 6 hours at room temperature. Rabbits blood disappearance was analyzed with biexponential model, T 1/2(α) =2 53min, T 1/2(β) =330min and Cl=378ml/hr. Biodistribution studies demonstrated that this radiopharmaceutical localized selectively in the myocardium of rats, the cardiac uptake was 4 69, 4 20, 3 95 and 3 43%ID/g at 5, 30, 60 and 90min postinjection, respectively, and the heart to lung activity ratio was 1 16 at 60min. Images showed pulmonary uptake was decreased faster than cardiac uptake in dogs, and the mean heart to lung activity ratio was 1 69, 2 40 and 2 55 at 10min, 30min and 60min postinjection, respectively. The heart was distinguishable on scans at 30min. Whole body imaging showed that cardiac uptake was 2 82%ID at 90min, but hepatic uptake was 30 13%ID and remained constant. The tolerance of this drug in mice was 614 times as much as in humans. [WT5”HZ]CONCLUSIONS 99m Tc NOEt exhibits favorable stability, biological property and safety. It is worth further studies in humans.

关 键 词：心肌显像剂 锝99M N(NOET)2 临床前药理研究 

分 类 号：R981.1[医药卫生—药品]