PET/MRI双模态显像剂68Ga-NOTA-SPIO的制备及其性质初步研究

摘要

目的 制备高灵敏度、高分辨率的PET/MRI双模态显像探针68Ga-NOTA-SPIO,对其体外及部分体内生物学性质进行评价,并探讨其作为PET/MRI双模态显像剂的可能.材料与方法 制备出前体SPIO-PEG2000-NOTA,并对其表征进行检测.采用“一锅法”对前体进行放射性标记,制备出双模态探针68Ga-NOTA-SPIO,采用快速薄层层析法测定标记率.评估其体外稳定性和脂水分配系数,并观察其在正常鼠的体内生物学分布.结果 制备出分散均一、粒径均匀的前体SPIO-PEG2000-NOTA;并合成双模态探针68Ga-NOTA-SPIO,标记率达99％,脂水分配系数Log P=-2.60±0.13,在磷酸盐缓冲液和胎牛血清中2h内的放化纯度均＞95％.小鼠体内生物分布实验显示,该探针主要分布于肝脏和脾脏,血液中廓清速度较快.结论 “一锅法”合成双模态探针68Ga-NOTA-SPIO标记率高、无需纯化,具有良好的理化性质及生物相容性,可用于后续的PET/MRI双模态显像研究.%Purpose To prepare 68Ga-NOTA-SPIO as PET/MRI dual mode imaging probe with high sensitivity and resolution,and further evaluate its in vitro and partly in vivo biological properties.Materials and Methods The precursor SPIO-PEG2000-NOTA was prepared and characterized.The precursor was radiolabeled by using "one step" method to prepare 68Ga-NOTA-SPIO as dual mode imaging probe.The labeling rate of the probe was determined by rapid thin-layer chromatography.Besides,the in vitro stability and lipid water partition coefficient of the probe were evaluated,and its biodistribution in normal mice was also observed.Results The precursor SPIO-PEG2000-NOTA with uniform dispersion and uniform particle size was prepared,and the dual mode probe 68Ga-NOTA-SPIO was synthesized.The labeling rate reached 99％,and the lipid water partition coefficient (Log P) was (-2.60±0.13).The radiochemical purity of the probe was higher than 95％,as it was incubated in the phosphate buffer and fetal bovine serum within 2 hours.The probe was mainly distributed in the liver and spleen of mice,and its clearance velocity in blood was fast.Conclusion The double mode probe 68Ga-NOTA-SPIO synthesized by one step method has high labeling rate with no need of purification,which has good physic-chemical properties and biocompatibility.The probe can be used in the further research of PET/MRI dual modality imaging.