A fluorinated dendrimer-based nanotechnology platform: new contrast agents for high field imaging.
A fluorinated dendrimer-based nanotechnology platform: new contrast agents for high field imaging.
复制标题
基于氟化树枝状聚合物的纳米技术平台：用于高场成像的新型造影剂。
DOI：
10.1097/rli.0b013e3181ee6e06
复制
发表时间：
2010
影响因子：
6.7
通讯作者：
Wiener,ErikC
中科院分区：
文献类型：
--
作者：
Huang,Zhihua;Sengar,RaghvendraS;Nigam,Archana;Abadjian,Marie-Caline;Potter,DouglasM;Grotjahn,DouglasB;Wiener,ErikC
目的：我们的目的是开发一种直接检测的磁共振成像（MRI）造影剂用于高场的基础上的纳米级氟化的树枝状聚合物为基础的平台为19 F MRI.Materials和方法的问题，克服了一些与19 F MRI.Materials的：树枝状聚合物制备在一个收敛的方式，使适当的树枝，然后耦合到一个中央核心。通过将3当量的氟化氨基酸连接到重复分支单元的3个羧酸上，然后将胺分支点脱保护，并偶联到另一个重复分支单元（增加G代）或直接使用以允许树枝状聚合物的精确生长来制备树枝状分子。通过扩散核磁共振（NMR）光谱法确定树枝状聚合物的尺寸。使用MTT测定来测量树枝状聚合物的毒性。在Bruker ACP-500 NMR上使用饱和恢复实验在470.59 MHz频率下进行氟纵向弛豫时间测量。结果：树枝状聚合物的粒径一般小于3 nm，比全氟化碳纳米颗粒的粒径（约200 nm）小2个数量级。的纵向弛豫时间，T1，随着树枝状聚合物代的增加而减小。松弛率和信噪比的显着改善，可以实现通过化学修饰的树枝状聚合物与钆螯合物或通过物理添加外源性造影剂。虽然在表面层中具有氟的树枝状聚合物是有毒的，但是通过将氟进一步埋入树枝状聚合物内部，这种毒性容易降低。19 F MR图像的大鼠使用的树枝状聚合物的解决方案，迅速获得在7特斯拉，在心脏中产生的强烈对比度的树枝状聚合物可以看到.Conclusions：一种新的氟化树枝状聚合物为基础的纳米技术平台在19 F MRI和一种新的双功能DOTA螯合物的制备和表征。我们介绍了2种减少19 F纵向弛豫时间的方法：（a）增加生成;（B）共价和非共价引入Gd（III）-螯合物。本文报道了一种新的双功能Gd（Ⅲ）螯合物。对大鼠的成像研究表明，树枝状聚合物在19 F MRI应用中具有潜在的重要性。
Objectives:We aimed to develop a directly detected magnetic resonance imaging (MRI) contrast agent for use with high fields based on a nanoscale fluorinated dendrimer-based platform for 19 F MRI and overcome some of the problems with 19 F MRI.Materials and Methods:The dendrimers were prepared in a convergent manner by making the appropriate dendron, followed by coupling to a central core. The dendrons were prepared by attaching 3 equivalents of the fluorinated amino acid to the 3 carboxylic acids of the repeat branch unit followed by deprotection of the amine branch point, and either coupling to another repeat branch unit (increasing the generation G) or used directly allowing the precise growth of the dendrimer. The size of the dendrimers was determined by diffusion nuclear magnetic resonance (NMR) spectroscopy. The toxicity of the dendrimers was measured using the MTT assay. Fluorine longitudinal relaxation time measurements were performed on a Bruker ACP-500 NMR using a saturation recovery experiment at 470.59 MHz frequency. Healthy 150 g Sprague-Dawley female rats were imaged using a dendrimer solution.Results:The size of the dendrimers is generally less than 3 nm, 2 orders of magnitude smaller than the size of the perfluorocarbon nanoparticles (about 200 nm). The longitudinal relaxation time, T 1, decreases with increasing dendrimer generation. A significant improvement in relaxation rate and signal-to-noise ratio can be achieved by either the chemical modification of the dendrimer with a gadolinium-chelate or by the physical addition of exogenous contrast agent. Although the dendrimers with fluorine in the surface layer are toxic, this toxicity is easily reduced by burying the fluorine further into the dendrimer interior. 19 F MR images of the rat using the dendrimer solution were rapidly obtained at 7 Tesla, the strong contrast in the heart generated by the dendrimer can be seen.Conclusions:A novel fluorinated dendrimer-based nanotechnology platform in 19 F MRI and a new bifunctional DOTA chelate were prepared and characterized. We introduce 2 methods for reducing the 19 F longitudinal relaxation time:(a) Increasing the generation;(b) covalent and noncovalent introduction of Gd (III)-chelates. A new bifunctional Gd (III)-chelate is presented. The investigations of imaging on rats suggest potential importance of the dendrimers in 19 F MRI application.