64Cu-DOTA-SPIONs-PEG-FA:靶向叶酸受体阳性肿瘤的PET/MRI双模态显像探针

摘要

报道了一种可用于叶酸受体阳性肿瘤显像的PET/MRI双模态显像探针(64Cu-DOTA-SPIONs-PEG-FA)的合成、初步的生物学评价及PET/CT和MRI显像结果.该探针由包覆了生物相容性的聚乙二醇(poly ethylene glycol,PEG)、超顺磁氧化铁纳米粒子(superparamegnetic iron oxide nanoparticles,SPIONs)、叶酸(folic acid,FA)、1,4,7,10-四乙酸-1,4,7,10-四氮杂环十二烷(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid,DOTA)和正电子放射性核素64Cu组成.经纯化后,64 Cu-DOTA-SPIONs-PEG-FA放化纯大于98％.荷KB裸鼠体内分布显示:64Cu-DOTA-SPIONs-PEG-FA在肝脏、脾脏和肺中的放射性摄取较高,与非靶向标记物64 Cu-DOTA-SPIONs-PEG-OH比较,其对KB细胞瘤有明显的靶向作用.在MRI和PET/CT 模式下,KB肿瘤能被较清晰地显像.64Cu-DOTA-SPIONs-PEG-FA作为KB细胞肿瘤的PET/MRI双模态显像剂,有待于进一步深入研究以改善其标记率、稳定性和比活度等.%The synthesis,preliminary biological evaluation and PET/CT and MRI imaging results of a potential PET/MRI dual-modal imaging tumor probe,64Cu-DOTA-SPIONsPEG-FA,used for targeting folate receptor-positive cancer,have been reported in this investigation.This probe was composed of a superparamagnetic iron oxide nanoparticles(SPIONs)coated with the biocompatible polymer poly(ethylene glycol)(PEG),folic acid,1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA) and positron-emitter copper-64.This radioactive probe has high radiochemical purity(greater than 98％) after purification.The bio-distribution in the nude mice bearing KB cells tumor shows that 64Cu-DOTA-SPIONs-PEG-FA has a higher uptake in liver,spleen and lung,respectively,and has an obvious effect of active targeting toward the KB tumor in contrast to 64Cu-DOTA-SPIONs-PEG-OH.Under the modes of both MRI and PET/CT,the KB tumor can be observed clearly.As a PET/MRI dual-modal imaging tumor probe,64Cu-DOTA-SPIONs-PEG-FA is worthy to be further studied to improve its labeling yield,stability,specific activity and so on.