超顺磁性氧化铁纳米粒子SPION-dopa-PEG-DOTA/RGD的^(64)Cu标记、纯化及生物分布

Radiolabeling of SPION-dopa-PEG-DOTA/RGD With ^(64)Cu and Biodistribution of the Radiolabel

对64 Cu标记超顺磁性氧化铁纳米粒子SPION-dopa-PEG-DOTA/RGD的标记及纯化条件进行探索,并根据其在小鼠体内的生物分布研究结果,揭示其主要的代谢方式。通过对标记过程中配体浓度、温度、时间等条件的改变,探究64 Cu标记SPION-dopa-PEG-DOTA/RGD的最优条件;并采用二乙基三胺五乙酸(DTPA)螯合标记混合物中游离的64 Cu,经PD-10柱纯化后得到放化纯较高的标记物;采用快速薄层层析法测定标记物的标记率和放化纯;分别测定了标记物的体外稳定性和脂水分配系数;将64 Cu标记的氧化铁纳米粒子经尾静脉注射到正常鼠的体内,分别于注射后不同时间点取各脏器,称重、测定放射性计数率,计算每克组织的百分注射剂量率(%ID/g)。经条件优化后得到的64 Cu-SPION-dopa-PEG-DOTA/RGD的标记率为63%,PD-10柱纯化后放化纯大于95%,水溶性良好,且放化纯在标记后12h内在磷酸盐缓冲液和人血清白蛋白中表现出了较高的稳定性;动物体内生物分布实验显示,该标记物在小鼠体内主要经肝脏代谢,肾脏排泄,血液中放射性清除较快。该标记物可用于后续的PET/MRI双模态显像的研究。

To investigate the construction and purification of the superparamagnetic iron oxide nanoparticles radiolabeled with 64 Cu and its biodistribution in mice,64Cu-SPION-dopaPEG-DOTA/RGD was prepared.To obtain a fair good radiolabeling yield and a high radio-chemical purity,the labeling conditions and purification method for 64Cu-SPION-dopa-PEGDOTA/RGD were optimized.Besides,stability in vitro and biodistribution studies in mice for 64Cu-SPION-dopa-PEG-DOTA/RGD were also studied.The labeling conditions were optimized and the radiolabeling yield is 63%.The radiochemical purity of 64Cu-SPION-dopaPEG-DOTA/RGD is more than 95% after purification.It is stable enough in the systems of PBS and HSA,respectively,within 12 hat room temperature.The octanol-water partition coefficients of 64Cu-SPION-dopa-PEG-DOTA/RGD(lg P)is-1.27.64Cu-SPION-dopaPEG-DOTA/RGD exhibites a relatively high uptake in liver and kindney and shows rapid clearance from blood based on the biodistribution studies.SPION-dopa-PEG-DOTA/RGD was radiolabeled with 64 Cu and purified successfully.64Cu-SPION-dopa-PEG-DOTA/RGD shows high stability in vitro.Biodistribution in vivo reveals the main metabolic pathway of this radiolabel,which can be further investigated acting as a PET/MRI dual-modal imaging agent.