^(177)Lu-DOTA/DTPA-Bz-Cys-RGD dimer的制备及正常鼠体内生物分布

Preparation of ^(177)Lu-DOTA/DTPA-Bz-Cys-RGD Dimer and Biodistribution Evaluation in Normal Mice

制备177Lu-DOTA-Bz-Cys-RGD dimer和177Lu-DTPA-Bz-Cys-RGD dimer,并对其体内外性质进行比较。TLC和HPLC分析结果表明,在pH=5.0和100℃条件下反应15~20 min,2种标记物的标记率均大于95%,并且在室温条件下2种标记物均保持良好的体外稳定性。HPLC分析结果和脂水分配系数lgP测定结果证实,177Lu-DOTA-Bz-Cys-RGD dimer的脂溶性高于177Lu-DTPA-Bz-Cys-RGD dimer。生物分布实验数据显示,注射后4 h,除了血液和脾,177Lu-DTPA-Bz-Cys-RGD dimer在其它组织中的摄取明显高于177Lu-DOTA-Bz-Cys-RGD dimer,177Lu-DOTA-Bz-Cys-RGD dimer的体内稳定性远好于177Lu-DTPA-Bz-Cys-RGD dimer。Bz-DOTA更适于作为双功能螯合剂用于RGD dimer的177Lu标记。

^177Lu-DOTA-Bz-Cys-RGD dimer and 177LuDTPA-Bz-Cys-RGD dimer were prepared,and the in vitro and in vivo properties were compared.TLC and HPLC show that the labeling yields of two radiolabeled compounds are more than 95% under optimal conditions（pH=5.0,reacting at 100 ℃ for 15-20 min）,and the two radiolabeled compounds show pretty good in vitro stability.HPLC analyses and lg P values reveal that lipophilicity of ^177Lu-DOTA-Bz-Cys-RGD dimer is higher than ^177Lu-DTPA-Bz-Cys-RGD dimer.The uptake of ^177Lu-DTPA-Bz-Cys-RGD dimer is other tissues is significantly higher than that of ^177Lu-DOTA-Bz-Cys-RGD dimer at 4h postinjection,except for blood and spleen.The in vivo stability of ^177Lu-DOTA-Bz-Cys-RGD dimer is much better than ^177Lu-DOTA-Bz-Cys-RGD dimer.Bz--DOTAis an ideal bifunctional chelator for ^177Lu labeling of RGD dimer.