Fluorescently detectable magnetic resonance imaging agents

Fluorescently detectable magnetic resonance imaging agents
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DOI:
10.1021/bc970153k
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发表时间:
1998-03-01
影响因子:
4.7
通讯作者:
Meade, TJ
Meade, TJ
中科院分区:
化学2区
文献类型:
--
作者:
Hüber, MM;Staubli, AB;Meade, TJ

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本报告描述了几种用于实验动物光学和磁共振成像 (MRI) 的双功能对比增强剂的合成、表征和体内测试。这些新试剂结合了两种技术的优点,因为它们可以通过光学和 MRI 显微镜同时观察。采用这种策略可以在截然不同的分辨率和深度下研究样本的相同生物结构。该配合物具有用于结合顺磁性离子钆 (Gd(3+)) 和共价连接的荧光染料的金属螯合剂。第一类复合物是低分子量物质,由大环四胺 1,4,7,10-四氮杂环十二烷-N,N',N",N'''-四乙酸 (DOTA) 作为金属螯合配体与四甲基罗丹明偶联。第二类 MRI 增强剂由膜不可渗透的高分子量聚合物组成,一旦注射到细胞或细胞中,这些复合物具有金属螯合剂二亚乙基三胺五乙酸 (DTPA) 和四甲基罗丹明的多个副本,这些副本附着在聚(D-赖氨酸)(pdl)或葡聚糖的大分子框架上,注射这些双功能药物后获得的单个细胞图像使我们能够跟踪非洲爪蟾原肠胚形成和神经形成过程中不同细胞层的相对运动和重组。胚胎。
This report describes the synthesis, characterization, and in vivo testing of several bifunctional contrast-enhancing agents for optical and magnetic resonance imaging (MRI) of experimental animals. These new agents integrate the advantages of both techniques since they can be visualized simultaneously by light and MRI microscopy. Employing this strategy allows the same biological structures of a specimen to be studied at dramatically different resolutions and depths. The complexes possess a metal chelator for binding a paramagnetic ion, gadolinium (Gd(3+)), and a covalently attached fluorescent dye. The first class of complexes are low-molecular weight species that are composed of the macrocyclic tetraamine 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid (DOTA) as the metal-chelating Ligand coupled to tetramethylrhodamine. The second class of MRI-enhancing agents are composed of high-molecular weight polymers that are membrane impermeable and once injected into a cell or cells are trapped inside. These complexes possess multiple copies of both the metal-chelator-diethylenetriaminepentaacetic acid (DTPA) and the tetramethylrhodamine attached to a macromolecular framework of either poly(D-lysine) (pdl) or dextran. Images acquired of single cells after injection with these bifunctional agents enabled us to follow the relative motions and reorganizations of different cell layers during amphibian gastrulation and neurulation in Xenopus laevis embryos.