RATIONALE AND APPLICATIONS FOR MACROMOLECULAR GD-BASED CONTRAST AGENTS
RATIONALE AND APPLICATIONS FOR MACROMOLECULAR GD-BASED CONTRAST AGENTS
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DOI：
10.1002/mrm.1910220225
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发表时间：
1991-12-01
影响因子：
3.3
通讯作者：
BRASCH, RC
中科院分区：
文献类型：
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作者：
BRASCH, RC
MRI用的大分子造影剂（MMCM）可以定义为具有足够分子量的顺磁性或超顺磁性化合物，通常为20 000道尔顿，表现出长时间的血管内滞留。相对较小的分子，如Gd-DTPA二聚氨胺（阳离子MW= 547道尔顿），可以在血液和血管外间质空间之间迅速平衡，而大分子MRI造影剂主要用于增强血池和内皮细胞异常通透性部位。在过去的几年中，我们的实验室和其他研究人员研究并比较了几种MMCM的性质，包括白蛋白-(Gd-DTPA) 30，葡聚糖-(Gd-DTPA) 15和聚赖氨酸-(Gd-DTPA) 50 （I-15）。表1简要比较了这些化合物的物理化学和药代动力学性质。具有增强血池潜力的其他制剂包括标记脂质体、颗粒和红细胞。表1中的每种化合物在大鼠体内的血浆半衰期至少为60分钟，有些化合物在60分钟或更长时间内对正常组织产生近乎恒定的增强作用。虽然主要的研究目标是确定一种优质的MMCM进行临床试验，但本文将重点介绍MMCM的独特特性以及通过体外和动物实验研究确定的潜在临床应用。完整的描述和详细的比较的竞争配方超出了这个摘要的范围。
Macromolecular contrast media (MMCM) for MRI may be defined as paramagnetic or superparamagnetic compounds of sufficient molecular weight, generally> 20,000 daltons, that demonstrate prolonged intravascular retention. As opposed to relatively smaller molecules, such as Gd-DTPA dimeglumine (cation MW= 547 daltons), which rapidly equilibrate between the blood and the extravascular interstitial space, macromolecular MRI contrast media are designed primarily to enhance the blood pool and sites of abnormal endothelial permeability. Over the past several years our laboratory and others have investigated and compared the properties of several MMCM including albumin-(Gd-DTPA) 30, dextran-(Gd-DTPA) 15, and polylysine-(Gd-DTPA) 50 (I-15). Physicochemical and pharmacokinetic properties of these compounds are briefly compared in Table 1. Additional formulations that have the potential to enhance the blood pool include labeled liposomes, particulates, and erythrocytes.Each of the compounds in Table 1 demonstrates a plasma half-life of at least 60 min in rats and some produce a near-constant enhancement of normal tissues for 60 min or longer. Although a major research goal is to identify a superior MMCM to carry forward into clinical trials, this summary will focus on unique characteristics of MMCM and on potential clinical applications defined by experimental studies in vitro and in animals. Complete characterizations and detailed comparison of contending formulations is beyond the scope of this summary.