体内分布
叶酸受体
体内
材料科学
赫拉
显像剂
正电子发射断层摄影术
离体
异硫氰酸荧光素
临床前影像学
磁共振成像
分子成像
体外
化学
荧光
核医学
癌症
癌细胞
生物化学
医学
生物
生物技术
放射科
内科学
量子力学
物理
作者
Jingyi Zhu,Hongsheng Li,Zhijuan Xiong,Mingwu Shen,Peter S. Conti,Xiangyang Shi,Kai Chen
标识
DOI:10.1021/acsami.8b12355
摘要
A Mn3O4 nanoparticle (NP)-based dual-modality probe has been developed for tumor positron emission tomography (PET)/magnetic resonance (MR) imaging. The dual-modality imaging probe was constructed by modifying multifunctional polyethyleneimine (PEI)-coated Mn3O4 NPs with folic acid (FA), followed with the radiolabeling with 64Cu. The formed imaging probe was utilized for PET/MR imaging of human cervical cancer mouse xenografts, which overexpress folate receptor (FR). The PEI-coated Mn3O4 NPs were synthesized using a solvothermal approach via decomposition of acetylacetone manganese. Multifunctional groups, including fluorescein isothiocyanate (FI), PEGylated FA, and NOTA chelator, were then sequentially loaded onto the surface of the amine groups of the Mn3O4 NPs. The remaining PEI amines were neutralized by the acetylation reaction. The resulting NOTA–FA–FI–PEG–PEI–Ac–Mn3O4 NPs were fully characterized and evaluated in vitro and successfully radiolabeled with 64Cu for tumor PET/MR imaging in small animals. In vivo blocking experiments were performed to determine the FR binding specificity of NPs. PET imaging results demonstrated that 64Cu-labeled Mn3O4 NPs display good tracer uptake in the FR-expressing HeLa tumors (tumor-to-muscle (T/M) ratio: 5.35 ± 0.31 at 18 h postinjection (pi)) and substantially reduced tracer uptake in the FR-blocked HeLa tumors (T/M ratio: 2.78 ± 0.68 at 18 h pi). The ex vivo data, including PET imaging and biodistribution, further confirmed the tumor binding specificity of the 64Cu-labeled Mn3O4 NPs. Moreover, the FR-targeted Mn3O4 NPs exhibited efficient T1-weighted MR imaging (MRI), leading to the precise tumor MRI at 18 h pi. PET/MR imaging with the 64Cu–NOTA–FA–FI–PEG–PEI–Ac–Mn3O4 NPs may offer a new quantitative approach to precisely measure the FR in tumors. The strategy of incorporating PEI nanotechnology into the construction of new biomaterials may be applied for the construction of novel nanoplatforms for cancer diagnosis and therapy.
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