Comparison of the macromolecular MR contrast agents with ethylenediamine-core versus ammonia-core generation-6 polyamidoamine dendrimer
Comparison of the macromolecular MR contrast agents with ethylenediamine-core versus ammonia-core generation-6 polyamidoamine dendrimer
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DOI：
10.1021/bc000075s
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发表时间：
2001-01-01
影响因子：
4.7
通讯作者：
Brechbiel, MW
中科院分区：
文献类型：
--
作者：
Kobayashi, H;Sato, N;Brechbiel, MW
两种新型大分子 MRI 造影剂基于假定分子大小相似但分子量不同的第 6 代聚酰胺胺树状聚合物 (G6)，在血液保留、组织分布和肾脏排泄方面进行了比较。使用具有氨核（G6A）或乙二胺核（G6E）的两个G6，其分别具有192和256个外部伯氨基。这些树枝状聚合物与2-(对异硫氰酸苄基)-6-甲基二亚乙基三胺五乙酸(1B4M)反应。 G6-IB4M 缀合物与 Gd-153 反应以研究生物分布和血液清除率，或与 Gd(III) 反应以进行 MRI 研究。使用 1.5-T 超导 MRI 装置注射 0.033 mmol Gd/kg 的 G6A-(1B4M-Gd)(192) 或 G6E-(1B4M-Gd)(256)，对小鼠进行 3D-micro-MR 血管造影。尽管使用 G6A-(1B4M-Gd)(192) 和 G6E-(1B4M-Gd)(256) 进行减影 3D-MR 血管造影时可以看到许多直径类似于 100 µm 的细血管，但 Gd-153 标记的饱和 G6E-(1B4M)(256) 在血液中的残留量明显多于 Gd-153 标记的饱和 G6E-(1B4M)(256)。注射后 15 分钟后的 G6A-(1B4M)(192) (p < 0.01)。此外，G6E-(IB4M-Gd)(256) 可视化这些更细的血管比 G6A-(1B4M-Gd)(192) 更长。与 G6E-(1B4M-Gd)(256) 相比，G6A-(1B4M-Gd)(192) 在动态 MR 图像上显示出更高的肾脏信号强度和更亮的肾脏图像。总之，尽管两种 G6-1B4M 缀合物具有几乎相似的分子大小和相同的化学结构，但观察到 G6A-(1B4M-Gd)(192) 比 G6E-(1B4M-Gd)(256) 更有效地通过肾小球滤过，从而导致更快的血液清除和更高的肾蓄积。就血管内造影剂的能力而言，G6E-(1B4M-Gd)(256)比G6A-(1B4M-Gd)(192)更好，因为每个分子有更多的Gd(III)原子，并且在循环中的保留时间更长。
Two novel macromolecular MRI contrast agents based upon generation-6 polyamidoamine dendrimers (G6) of presumed similar molecular size, but of different molecular weight, were compared in terms of their blood retention, tissue distribution, and renal excretion. Two G6s with either ammonia core (G6A) or with ethylenediamine core (G6E), which possessed 192 and 256 exterior primary amino groups, respectively, were used. These dendrimers were reacted with 2-(p-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid (1B4M). The G6-IB4M conjugates were reacted with Gd-153 for studying biodistribution and blood clearance or Gd(III) for the MRI study. 3D-micro-MR angiography of the mice were taken with injection of 0.033 mmol of Gd/kg of G6A-(1B4M-Gd)(192) or G6E-(1B4M-Gd)(256) using a 1.5-T superconductive MRI unit. Although numerous fine vessels of similar to 100 mum diameter were visualized on subtracted 3D-MR-angiography with both G6A-(1B4M-Gd)(192) and G6E-(1B4M-Gd)(256), Gd-153-labeled saturated G6E-(1B4M)(256) remained in the blood significantly more than Gd-153-labeled saturated G6A-(1B4M)(192) at later than 15 min postinjection (p < 0.01). In addition, G6E-(IB4M-Gd)(256) visualized these finer vessels longer than G6A-(1B4M-Gd)(192). The G6A-(1B4M-Gd)(192) showed higher signal intensity in the kidney on the dynamic MR images and brighter kidney images than G6E-(1B4M-Gd)(256). In conclusion, the G6A-(1B4M-Gd)(192) was observed to go through glomerular filtration more efficiently than G6E-(1B4M-Gd)(256) resulting faster clearance from the blood and higher renal accumulation, even though both of G6-1B4M conjugates have almost similar molecular size and same chemical structure. In terms of the ability of intravascular contrast agents, G6E-(1B4M-Gd)(256) was better due to more Gd(III) atoms per molecule and longer retention in the circulation than G6A-(1B4M-Gd)(192).