99Tcm-HMIBP的生物学特性及与99Tcm-MDP的骨显像比较

目的 通过99Tcm-1-羟基-2-(1-甲基咪唑-2-基)乙烷-1,1-二膦酸(HMIBP)和鲫99Tcm-亚甲基二膦酸盐(MDP)的骨显像质量比较,评价99Tcm-HMIBP作为骨显像剂的可能性.方法 制备HMIBP冻干药盒,对HMIBP及SnCl2-2H2O含量、放化纯、药盒pH值及在4℃下的稳定性等进行了研究.测定99Tcm-HMIBP在正辛醇/水相中的分配系数(P)及血浆蛋白结合率,计算血药清除动力学方程参数.同时研究了HMIBP的半数致死剂量(LD50).新西兰兔静脉注射99Tcm-HMIBP和99Tcm-MDP后同步显像比较.结果 99Tcm-HMIBP药盒含HMIBP 5 mg,SnCl2·2H2O 0.05 mg,药盒pH值为5,标记率和放化纯均为98%;在4℃下放置180 d后标记率为96%.在pH值为7.0和7.4时,P值分别为0.0125和0.0054,血浆蛋白结合率为44.77%.小鼠血药清除动力学方程为C=3.0979 e-0.0721t+0.1250 e-0.0076.HMIBP的LD50为8.2 mg/kg.兔骨显像表明,99Tcm-HMIBP和99Tcm-MDP在3 h时均可获得清晰的图像.结论 99Tcm-HMIBP生物学性能优良,显像效果与99Tcm-MDP相当,可能成为集显像与治疗于一体的骨显像剂.

Biological properties of 99Tcm-HMIBP and its usefulness for bone scintigraphy by comparing with 99Tcm-MDP imaging

Objective Zoledronate has been extensively used for the treatment of tumor-induced hypercalcemia and osteolytic bone metastases.1-hydroxy-2-(1-methylimidazol-2-yl)ethylidene-1,1-bisphos-phonic acid(HMIBP)with similar chemical structure as Zoledronate,was therefore considered to be useful as bone imaging agent.In this study the usefulness of 99Tcm labeled HMIBP for bone imaging was evaluated and the results with the well-established 99Tcm-methylene diphosphonic acid(MDP)imaging was compared.Methods Labeled with 99Tcm,the SnCl2·2H2O quantity,radiochemical purity,pH value and stability at 4℃ of 99Tcm-HMIBP were measured.Besides,the partition coefficient,plasma protein binding rate,hemody-namic parameters of 99Tcm-HMIBP and median lethal dose(LD50)of HMIBP were determined.99Tcm-HMIBP bone imaging was performed in normal New Zealand rabbits and compared with 99Tcm-MDP bone imaging.Results The kit composed of 5 mg HMIBP and 0.05 mg SnCl2·2H2O.The labeling rate was 96% after 180 d storage at 4℃.The radiochemical purity of 99Tcm-HMIBP was 98% at pH 5 and the partition coefficients were 0.0125 and 0.0054 at pH 7.0 and 7.4 respectively.The plasma protein binding rate of 99Tcm-HMIBP was 44.77%.The hemedynamic parameter C valued 3.0979 e-0.0721t+0.1250 e-0.0076 and LD50 was 8.2 mg/kg.The bone images of 99Tcm-HMIBP were fairly well 3 h after the injection.which was comparable to 99Tcm-MDP bone imaging.Conclusions 99Tcm-HMIBP had good biological properties and comparable bone imaging quality with 99Tcm-MDP.It might be a potential agent for both treatment and imaging.