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

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

  • 摘要: 制备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以及标记化合物体外稳定性的影响,以及对标记化合物的药代动力学性质和小鼠体内生物分布的影响。TLC和HPLC分析结果表明,在pH 6.0和pH 4.0条件下100℃反应15-20 min,两种标记化合物的标记率均大于95%,并在生理盐水体系中,二者均保持良好的稳定性。HPLC的分析结果和脂水分配系数 log Pow的测定结果显示177Lu-DOTA-Bz-PEG4-RGD dimer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和小鼠的体内生物分布。

     

    Abstract: 177 Lu DOTA Bz RGD dimer and  177 Lu 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 lg P ow 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.

     

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