Macromolecular MRI contrast agents with small dendrimers: Pharmacokinetic differences between sizes and cores
Macromolecular MRI contrast agents with small dendrimers: Pharmacokinetic differences between sizes and cores
复制标题
DOI：
10.1021/bc025633c
复制
发表时间：
2003-03-01
影响因子：
4.7
通讯作者：
Star, RA
中科院分区：
文献类型：
--
作者：
Kobayashi, H;Kawamoto, S;Star, RA
具有白蛋白或树枝状聚合物核的大分子MRI造影剂可用于血管成像。然而，它们的长期保留是临床使用的主要限制。尽管较小的基于树枝状聚合物的MRI造影剂更快地由肾脏排出，但由于外渗较少，它们也能够比Gd-DTPA更好地可视化血管结构。此外，与Gd-DTPA不同，它们在肾小管中短暂蓄积，因此也可用于可视化肾脏结构和功能损伤。然而，这些树枝状聚合物剂在体内保留很长时间。本研究的目的是获得信息，从这些信息中可以选择适用于进一步临床研究的基于大分子树枝状聚合物的MRI造影剂。合成了六种基于小树枝状聚合物的MRI造影剂，并在小鼠中评价了它们的药代动力学、全身保留和动态MRI，以确定与Gd-[DTPA]-二甲葡胺相比的最佳药剂。基于二氨基丁烷（DAB）树枝状聚合物的药剂比具有相同数目的分支的基于聚酰胺胺（PAMAM）树枝状聚合物的药剂更快地从体内清除。较小的树枝状聚合物缀合物比较大的树枝状聚合物缀合物更迅速地从体内排泄。由于基于PAMAM-G2、DAB-G3和DAB-G2树枝状聚合物的造影剂显示出相对快速的排泄，因此这三种缀合物可用于进一步的临床应用。
Large macromolecular MRI contrast agents with albumin or dendrimer cores are useful for imaging blood vessels. However, their prolonged retention is a major limitation for clinical use. Although smaller dendrimer-based MRI contrast agents are more quickly excreted by the kidneys, they are also able to visualize vascular structures better than Gd-DTPA due to less extravasation. Additionally, unlike Gd-DTPA, they transiently accumulate in renal tubules and thus also can be used to visualize renal structural and functional damage. However, these dendrimer agents are retained in the body for a prolonged time. The purpose of this study was to obtain information from which a macromolecular dendrimer-based MRI contrast agents feasible for use in further clinical studies could be chosen. Six small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole-body retention, and dynamic MRI were evaluated in mice to determine an optimal agent in comparison to Gd-[DTPA]-dimeglumine. Diaminobutane (DAB) dendrimer-based agents cleared more rapidly from the body than polyamidoamine (PAMAM) dendrimer-based agents with the same numbers of branches. Smaller dendrimer conjugates were more rapidly excreted from the body than the larger dendrimer conjugates. Since PAMAM-G2, DAB-G3, and DAB-G2 dendrimer-based contrast agents showed relatively rapid excretion, these three conjugates might be acceptable for use in further clinical applications.