Gadolinium(III) di- and tetrachelates designed for in vivo noncovalent complexation with plasma proteins: a novel molecular design for blood pool MRI contrast enhancing agents.
Gadolinium(III) di- and tetrachelates designed for in vivo noncovalent complexation with plasma proteins: a novel molecular design for blood pool MRI contrast enhancing agents.
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钆（III）二螯合物和四螯合物设计用于与血浆蛋白体内非共价络合：血池 MRI 对比增强剂的新型分子设计。
DOI：
10.1021/bc00035a017
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发表时间：
1995
影响因子：
4.7
通讯作者：
Keana,JF
中科院分区：
文献类型：
--
作者：
Martin,VV;Ralston,WH;Hynes,MR;Keana,JF
顺磁性物质由于其能够缩短附近水质子的弛豫时间而在生物和医学磁共振成像（MRI）应用中广泛用作对比度增强剂（1）。由于每个Gd（III）离子中存在7个未成对电子和较长的电子自旋弛豫时间（2），Gd（III）的络合物特别有吸引力。与其他顺磁性过渡离子或有机稳定自由基相比，Gd（III）螯合物提供最大的摩尔弛豫率。设计用于对血池成像的造影剂必须在血管系统中保留至少30分钟以允许图像采集。通过肾脏肾小球的过滤，血池因子的分子量大于20 000（1，3）。已经开发并测试了几种大分子造影剂用于血池MRI应用。这些试剂含有多个Gd-螯合部分，其形式为与二亚乙基三胺五乙酸（DTPA）残基共价连接到大分子载体的络合物。各种天然和合成聚合物已被用作载体，包括血清白蛋白（3），聚赖氨酸（PL）（3），聚赖氨酸-聚（乙二醇）共轭物（MPEG-PL）（4），和功能化葡聚糖（3，5，6）。沿着在脉管系统中相对较长的保留时间（1-4 h，相比之下，Gd-DTPA为15-20 min）（3），大分子缀合物显示分子弛豫率跳跃至每个Gd（III）离子15 L-mmol-1 ^-1，相比之下，Gd-DTPA络合物本身约为6 L-mmol-1 ^-1（2，3）。这种所谓的质子弛豫率增强效应（PRE）（7）归因于共轭顺磁单元相对于自由顺磁单元（3，8）的更低、更优化的翻滚速率。
Paramagnetic species enjoy wide use as contrast enhancing agents in biological and medical magnetic resonance imaging (MRI) applications owing to their ability to shorten the relaxation time of nearby water protons (1). Complexes of Gd (III) are particularly at-tractive owing to the presence of seven unpaired electrons in each Gd (III) ion and a long electron spin relaxation time (2). Compared to other paramagnetic transition ions or organic stable radicals, Gd (III) chelates provide maximum molar relaxivity.Contrast agents designed to image the blood pool must remain in the vasculature for at least 30 min to allow for image acquisition. Filtration by the glomeruli in the kidney defines the molecularweight of blood pool agents to be> 20 000 (1, 3). Several macromolecular contrast agents have been developed and tested for blood pool MRI applications. These reagents contain multiple Gd-che-lated moieties in the form of complexes with diethylenetriaminepentaacetic acid (DTPA) residues covalently linked to a macromolecular carrier. Various natural and synthetic polymers havebeen employed as carriers including serum albumin (3), polylysine (PL)(3), polyl-ysine-poly (ethylene glycol) conjugate (MPEG-PL)(4), and functionalized dextrans (3, 5, 6). Along with rela-tively long retention times in the vasculature (1-4 h, compared to 15—20 min for Gd—DTPA)(3) the macro-molecular conjugates display a jump in molecular relax-ivity up to 15 L-mmol-1^'1 per Gd (III) ion compared to about 6 L-mmoL^ s'1 for the Gd—DTPA complex itself (2, 3). This so-called proton relaxivity enhancement effect (PRE)(7) is attributed to a lower, more optimal tumbling rate of the conjugated versus free paramagnetic unit (3, 8).