^(177)Lu-DOTA-Bz-RGD dimer和^(177)Lu-DOTA-Bz-PEG4-RGD dimer的制备及生物评价  

Preparation and Evaluation of ^(177)Lu-DOTA-Bz-RGD dimer and ^(177)Lu-DOTA-Bz-PEG4-RGD dimer

作　　者：史继云[1] 余子璘[1] 贾兵[1] 赵慧云[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4期214-218,223,共6页Journal of Isotopes

基　　金：北京市科技计划项目(Z00004105040311)

摘　　要：制备了177Lu-DOTA-Bz-RGD dimer和177Lu-DOTA-Bz-PEG4-RGD dimer,并比较4个PEG分子的引入对标记条件标记化合物体外稳定性、标记化合物的药代动力学性质及其在小鼠体内生物分布的影响。薄层色谱法(TLC)和高效液相色谱法(HPLC)分析结果表明,反应液pH分别为4.0和6.0时,100℃反应15~20 min,两种标记化合物的标记率均>95%。在生理盐水体系中,二者均保持良好的稳定性,放置72 h放化纯度仍>90%。HPLC的分析结果和脂水分配系数lgPow的测定结果显示,177Lu-DOTA-Bz-PEG4-RGDdimer的脂溶性有所提高。引入4个PEG分子没有显著改变标记化合物的药代动力学性质及其在小鼠体内的生物分布。^177Lu-DOTA-Bz-RGD dimer and ^177Lu-DOTA-Bz-PEG4-RGD dimer were prepared, and the effect of PEG4 on labeling conditions and in vitro stability as well as pharmacokinetic properties and biodistribution in normal mice for the radiolebeled compounds was compared. The results of TLC and HPLC show that the labeling yield of two radiolabeled compounds was more than 95% under optimal conditions （pH 4.0 and pH 6.0, respectively, reacting at 100 ℃ for 15-20 min）. The two radiolabeled compounds show pretty good stability in saline. HPLC analyses and lgPow values revealed that introducing of PEG4 increased the lipophilic character of radiolabeled compounds, but had no significant changes on pharmacokinetic properties and biodistribution in normal mice.

关 键 词：^177Lu RGD二聚体 PEG 标记 生物分布 

分 类 号：TQ463[化学工程—制药化工] R817-33[医药卫生—影像医学与核医学]