Development of Intravascular Contrast Agents for MRI Using Gadolinium Chelates
Development of Intravascular Contrast Agents for MRI Using Gadolinium Chelates
复制标题
DOI：
10.1002/cmdc.201100066
复制
发表时间：
2011-05-02
期刊：
影响因子：
3.4
通讯作者：
Bates, Roderick W.
中科院分区：
文献类型：
--
作者：
Kittigowittana, Krisada;Yang, Chang-Tong;Bates, Roderick W.
两种MRI造影剂（CA）组成的Gd-DO 3A共轭衍生自谷氨酸（CA 1）和赖氨酸（CA 2）的氨基酸结构单元已通过使用新的炔和丙酸酯连接体合成，并随后进行了表征。体外细胞活力测定表明，在低浓度（最高0.2 mm）下，两种CA的细胞毒性不显著。在25 ℃的H2O中，在9.4 T下测量的CA 1和CA 2的纵向弛豫率（r（1））分别为6.4和5.4 mm（-1）s（-1）。两个r（1）值均高于临床用途：Gd-DTPA（Magnevist，Bayer Schering，德国）和Gd-DOTA（Dotarem，Guerbet，法国）的CA值。在Wistar大鼠体内成像表明，相当大的信号增强（类似于50%），在脑动脉的CA 2，但较低的信号增强（类似于30%）的CA 1。与多它灵相比，多它灵显示出与CA 2相似的信号增强，即使在注射后52分钟，CA 2的增强仍然很高（类似于30%）。这表明CA 2具有更长的血液半衰期（68.1分钟），这可能有利于血管造影和组织靶向。
Two MRI contrast agents (CAs) composed of Gd-DO3A conjugated to amino acid building blocks derived from glutamic acid (CA1) and lysine (CA2) have been synthesized by using novel alkyne and propionate linkers, and subsequently characterized. In vitro cell viability assays showed insignificant cytotoxicity of both CAs at low concentrations up to 0.2 mm. The longitudinal relaxivities (r(1)) of CA1 and CA2 measured at 9.4 T are 6.4 and 5.4 mm(-1) s(-1) in H(2)O at 25 degrees C, respectively. Both r(1) values are higher than those of CAs in clinical use: Gd-DTPA (Magnevist, Bayer Schering, Germany) and Gd-DOTA (Dotarem, Guerbet, France). In vivo imaging in Wistar rats demonstrated considerable signal enhancement (similar to 50%) in the brain artery by CA2, but lower signal enhancement (similar to 30%) by CA1. In contrast to Dotarem, which showed a similar signal enhancement as CA2, the enhancement by CA2 remained high (similar to 30%), even at 52 min post-injection. This demonstrates that CA2 has a much longer blood half-life (68.1 min), which could be advantageous for angiography and tissue targeting.