Kobayashi H, Sato N, Kawamoto S, Saga T, Hiraga A, Haque T L, Ishimori T, Konishi J, Togashi K, Brechbiel M W
Hitachi Medical Co. chaired Department of Diagnostic and Interventional Imagiology, Kyoto University, Kyoto 606-8507, Japan.
Bioconjug Chem. 2001 Jan-Feb;12(1):100-7. doi: 10.1021/bc000075s.
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-methyl-diethylenetriaminepentaacetic acid (1B4M). The G6--1B4M conjugates were reacted with (153)Gd 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 approximately 100 microm diameter were visualized on subtracted 3D-MR-angiography with both G6A--(1B4M-Gd)(192) and G6E--(1B4M-Gd)(256), (153)Gd-labeled saturated G6E-(1B4M)(256) remained in the blood significantly more than (153)Gd-labeled saturated G6A--(1B4M)(192) at later than 15 min postinjection (p < 0.01). In addition, G6E--(1B4M-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).
比较了两种基于第6代聚酰胺-胺树枝状大分子（G6）的新型大分子磁共振成像（MRI）造影剂，它们假定分子大小相似，但分子量不同，对其血液滞留、组织分布和肾排泄情况进行了比较。使用了两种分别以氨为核心（G6A）和以乙二胺为核心（G6E）的G6，它们分别具有192个和256个外部伯氨基。这些树枝状大分子与2-（对异硫氰酸苄基）-6-甲基二乙烯三胺五乙酸（1B4M）反应。G6-1B4M共轭物与（153）Gd反应以研究生物分布和血液清除情况，或与钆（III）反应用于MRI研究。使用1.5-T超导MRI设备，以0.033 mmol钆/千克的剂量注射G6A-（1B4M-Gd）（192）或G6E-（1B4M-Gd）（256）后，对小鼠进行三维显微磁共振血管造影。尽管在使用G6A-（1B4M-Gd）（192）和G6E-（1B4M-Gd）（256）进行的三维减影磁共振血管造影上都能看到许多直径约100微米的细小血管，但在注射后15分钟后，（153）Gd标记的饱和G6E-（1B4M）（256）在血液中的残留量明显多于（153）Gd标记的饱和G6A-（1B4M）（192）（p<0.01）。此外，G6E-（1B4M-Gd）（256）显示这些较细血管的显影时间比G6A-（1B4M-Gd）（192）长。在动态磁共振图像上，G6A-（1B4M-Gd）（192）在肾脏中的信号强度高于G6E-（1B4M-Gd）（256），肾脏图像也更亮。总之，尽管两种G6-1B4M共轭物的分子大小几乎相似且化学结构相同，但观察到G6A-（1B4M-Gd）（192）比G6E-（1B4M-Gd）（256）更有效地通过肾小球滤过，导致其从血液中清除更快且肾脏蓄积更高。就血管内造影剂的能力而言，G6E-（1B4M-Gd）（256）更好，因为其每个分子中的钆（III）原子更多，且在循环中的保留时间比G6A-（1B4M-Gd）（192）长。
