^99Tc^m-HMIBP的生物学特性及与^99Tc^m-MDP的骨显像比较  

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

作　　者：罗世能[1] 郭雪花 叶万忠[1] 谢敏浩[1] 周莲 虞燕华[1] 赵燕[1] 曹国宪[1] 

机构地区：[1]江苏省原子医学研究所、卫生部核医学重点实验室,江苏省无锡市214063 [2]江南大学化学与材料工程学院

出　　处：《中华核医学杂志》2008年第4期231-233,共3页Chinese Journal of Nuclear Medicine

基　　金：吴阶平医学基金会临床科研专项资助基金（320.6750.06115）

摘　　要：目的通过^99Tc^m-1-羟基-2-（1-甲基咪唑-2-基）乙烷-1，1-二膦酸（HMIBP）和^99Tc^m-亚甲基二膦酸盐（MDP）的骨显像质量比较，评价^99Tc^m 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^99Tc^m-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^99Tc^m-HMIBP和^99Tc^m-MDP后同步显像比较。结果^99Tc^m-HMIBP药盒含HMIBP5mg，SnCl2·2H2O0．05mg，药盒pH值为5，标记率和放化纯均为98％；在4℃下放置180d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=3．0979e^-0.0721t＋0．1250e^-0.0076t-HMIBP的LD50为8．2mg／kg。兔骨显像表明，^99Tc^m-HMIBP和^99Tc^m-MDP在3h时均可获得清晰的图像。结论^99Tc^m-HMIBP生物学性能优良，显像效果与^99Tc^m-MDP相当，可能成为集显像与治疗于一体的骨显像剂。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-bisphosphonic acid （HMIBP） with similar chemical structure as Zoledronate, was therefore considered to be useful as bone imaging agent. In this study the usefulness of ^99Tc^m-labeled HMIBP for bone imaging was evaluated and the results with the well-established ^99Tc^m-methylene diphosphonic acid （MDP） imaging was compared. Methods Labeled with ^99Tc^m- the SnC12 · 2H2O quantity, radiochemical purity, pH value and stability at 4℃ of ^99Tc^m-HMIBP were measured. Besides, the partition coefficient, plasma protein binding rate, hemody- namic parameters of ^99Tc^m-HMIBP and median lethal dose （LDso） of HMIBP were determined. 99Tcm-HMIBP bone imaging was performed in normal New Zealand rabbits and compared with ^99Tc^m-MDP bone imaging. Results The kit composed of 5 mg HMIBP and 0.05 mg SnC12· 2H2O. The labeling rate was 96% after 180 d storage at 4℃. The radiochemical purity of ^99Tc^m-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 9^99Tc^m-HMIBP was 44. 77%. The hemodynamic parameter C valued 3.0979e^-0.0721t＋0.1250e^-0.0076t and LD50 was 8.2 mg/kg. The bone images of ^99Tc^m-HMIBP were fairly well 3 h after the injection, which was comparable to ^99Tc^m-MDP bone imaging. Conclusions ^99Tc^m-HMIBP had good biological properties and comparable bone imaging quality with ^99Tc^m-MDP. It might be a potential agent for both treatment and imaging.

关 键 词：HMIBP 同位素标记 动物 实验 药代动力学 骨骼 放射性核素显像 MDP 

分 类 号：R686[医药卫生—骨科学]