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铜激活的 MRI/PET 成像造影剂的细胞标记效率、细胞毒性和弛豫率。

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents.

机构信息

Steacie Institute for Molecular Science, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, Canada K1A 0R6.

出版信息

Biomaterials. 2011 Feb;32(4):1167-76. doi: 10.1016/j.biomaterials.2010.10.013. Epub 2010 Oct 28.

DOI:10.1016/j.biomaterials.2010.10.013
PMID:21035183
Abstract

A new class of nanoparticle-based dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI) contrast agents has been developed. The probe consists of a superparamagnetic iron oxide (SPIO) or manganese oxide core coated with 3,4-dihydroxy-D,L-phenylalanine (DL-DOPA). The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to DOPA termini. The DOTA modified nanoparticles allow chelation of copper for PET imaging. These surface functionalized nanoparticle-based probes have been characterized by various analytical techniques. The cell-labeling efficacy, cytotoxicity and relaxivity of these nanoparticles have been evaluated and compared with the same properties of one of the most commonly utilized MRI contrast agents, Feridex(®). Evidently, this new nanoparticle has a great potential for use in cell tracking with MRI and PET in the absence of transfecting agent. It is noteworthy that there is a sharp increase in r(2) relaxivity of these nanoparticles on coordination with Cu(2+) ions. Thus these iron oxide nanoparticles can also be explored as the smart magnetic resonance (MR) sensor for the detection of micromolar changes in copper concentration for neurodegenerative diseases such as Alzheimer's disease, Menkes and Wilson's diseases, amyotrophic lateral sclerosis and prion diseases.

摘要

一种新型基于纳米粒子的正电子发射断层扫描/磁共振成像(PET/MRI)双模态对比剂已经被开发出来。该探针由超顺磁性氧化铁(SPIO)或氧化锰核组成,表面覆盖有 3,4-二羟基-D,L-苯丙氨酸(DL-DOPA)。螯合剂 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)连接到 DOPA 末端。DOTA 修饰的纳米粒子允许螯合铜以进行 PET 成像。这些表面功能化的基于纳米粒子的探针已经通过各种分析技术进行了表征。已经评估了这些纳米粒子的细胞标记效率、细胞毒性和弛豫率,并将其与最常用的 MRI 对比剂之一 Feridex(®)的相同性质进行了比较。显然,这种新的纳米粒子在没有转染剂的情况下,在使用 MRI 和 PET 进行细胞跟踪方面具有很大的潜力。值得注意的是,这些纳米粒子与 Cu(2+)离子配位时 r(2)弛豫率显著增加。因此,这些氧化铁纳米粒子也可以作为智能磁共振(MR)传感器,用于检测神经退行性疾病(如阿尔茨海默病、Menkes 和 Wilson 病、肌萎缩侧索硬化症和朊病毒病)中铜浓度的微摩尔变化。

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