^(99)Tc^m-HYNIC-β-Ala-BBN(7-14)NH_2的制备及其初步生物分布  

Preparation and Preliminary Evaluation of ^(99)Tc^m-HYNIC-β-Ala-BBN(7-14)NH_2

作　　者：全欣[1] 张燕[1] 贾兵[1] 赵慧云[1] 余子璘[1] 史纪云[1] 王凡[1] 

机构地区：[1]北京大学医学同位素研究中心

出　　处：《同位素》2007年第2期77-82,共6页Journal of Isotopes

基　　金：北京市科技计划项目(Z00004105040311)

摘　　要：分别选用Tricine和EDDA作为协同配体制备了99Tcm-HYNIC-β-Ala-BBN(7-14)NH2,并比较了两种标记物的体外稳定性和体内生物分布。ITLC和HPLC分析结果表明,两种标记物的标记率均大于95%,经Sep-Pak C-18柱纯化后,其放化纯度均大于99%。在生理盐水和牛血清体系中,两种标记物均保持良好的稳定性,但在半胱氨酸体系中,99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2具有更好的稳定性,37℃下孵育24 h,其放化纯度仍大于95%;而在相同条件下,99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2的放化纯度已低于90%。血液清除实验表明,99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2和99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2均符合二室代谢模型,其分布相半衰期分别为0.27 min和1.55 min,消除相半衰期分别为18.1 min和29.7 min。生物分布数据显示,99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2每个时间点所有脏器中的放射性摄取均高于99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2;两者在肾脏中的摄取均较高,99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2在肝脏和肠中的放射性摄取显著高于99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2,说明99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2主要通过肾脏排泄,而99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2既通过肾脏排泄,同时也有相当一部分标记物通过肝胆排泄。以上实验数据表明,99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2具有更好的化学和生物学性质,值得进一步研究。^99Tc^m-HYNIC-β-AIa-BBN（7-14）NH2 is prepared by choosing Tricine and EDDA as coligands, and the in vitro stability and biodistribution are compared for the two compounds. The results of ITLC and HPLC analyses show that the labeling yield of both compounds is〉 95%, and the radiochemical purity （RCP） after purification of Sep-Pak C-18 cartridge is 99 %. Both of the compounds show pretty good stability in saline and fetal bovine serum, but cysteine challenge assay shows that the stability of ^99Tc^m-HYNIC（EDDA）-β-Ala-BBN （7-14） NH2 is much better than 99 Tcm HYNIC （ Tricine）-β-Ala-BBN （7-14） NH2, with the RCP is 〉95% and 〈90%, respectively, at 24 h incubation at 37℃. Pattern of blood clearance of ^99Tc^m-HYNIC （ EDDA）-β-Ala-BBN （7-14） NH2 and ^99Tc^m-HYNIC （Tricine）-β-Ala-BBN（7-14）NH2 is defined as two-compartment model, with T（1/2a）. calculated to be 0.27 min and 1.55 min, and T（1/2a） calculated to be 18.1 min and 29.7 min, respectively. Biodistribution reveals that the radio uptake of 99Tc^m-HYNIC（Tricine）-β-Ala-BBN（7- 14）NH2 is higher than that of 99Tc^m-HYNIC（EDDA）-β-Ala-BBN（7-14）NH2 for all of tissues at all time points of the experiment. The uptake in kidneys for both compounds is relatively high, as the uptake in livers and intestines for 699Tc^m-HYNIC（Tricine）-β-Ala-BBN（7- 14）NH2 is significantly higher than that for ^99Tc^m-HYNIC（EDDA）-β-Ala-BBN（7-14）NH2, which means that ^99Tc^m-HYNIC（EDDA）-β-Ala-BBN（7-14）NH2 is mainly excreted through kidneys, while ^99Tc^m-HYNIC（Tricine）-β-Ala-BBN（7-14）NH2 is excreted through both kidneys and hepatobiliary system. The above data demonstrate that ^99Tc^m-HYNIC（EDDA）-β- Ala-BBN（7-14）NH2 possesses better chemical and biological properties.

关 键 词：^99TC^M 蛙皮素(BBN) 协同配体 

分 类 号：TQ463.7[化学工程—制药化工] R817[医药卫生—影像医学与核医学]