Institut de Physique et Chimie des Matériaux de Strasbourg - Groupe des Matériaux Organiques, 23 Rue du Loess BP 43, 67034 Strasbourg Cedex 2, France.
Toxicol In Vitro. 2010 Aug;24(5):1386-94. doi: 10.1016/j.tiv.2010.05.001. Epub 2010 May 10.
Interest in contrast agent's (CA) neurotoxicity has greatly increased due to the growing need of new compounds dedicated to brain imaging. Magnetic resonance imaging (MRI) CA have been evaluated by means of different toxicological assays with cultured rat primary neurons (evaluation of neurite specific parameters via immunostaining of the cells and LDH leakage). To determine the potential neurotoxicity of a precise paramagnetic ion in a defined structure (architecture and molecular weight), novel hydrosoluble dendritic Manganese (II) and Gadolinium (III) complexes derived from diethylenetriamine pentaacetic acid (DTPA) have been studied and compared to a linear homologue (same molecular weight) and commercially available low molecular weight MRI CA like Mn-DPDP (Teslascan, GE Healthcare) and Gd-DTPA (Magnevist, Schering). The range of CA concentrations studied was 0.1-10mM, suitable for MRI examinations. This set of experiments allows a toxicity ranking of these reagents as a function of molecular structure and nature of the paramagnetic ion. We could determine that the architecture (linear vs. dendritic) does not play an important role in the in vitro neurotoxicity, whereas the structure of the chelating cage is of greater importance.
由于对专门用于脑成像的新化合物的需求不断增长，人们对造影剂（CA）的神经毒性的兴趣大大增加。通过使用不同的毒理学测定方法对培养的大鼠原代神经元进行了磁共振成像（MRI）CA 的评估（通过细胞免疫染色和 LDH 渗漏评估神经突特异性参数）。为了确定特定结构（架构和分子量）中精确的顺磁离子的潜在神经毒性，研究并比较了新型水溶性树枝状锰（II）和钆（III）复合物，其来源于二乙三胺五乙酸（DTPA），并与线性同系物（相同分子量）和市售低分子量 MRI CA 如 Mn-DPDP（Teslascan，GE Healthcare）和 Gd-DTPA（Magnevist，Schering）进行了比较。研究的 CA 浓度范围为 0.1-10mM，适用于 MRI 检查。这组实验可以根据分子结构和顺磁离子的性质对这些试剂的毒性进行排序。我们可以确定，架构（线性与树枝状）在体外神经毒性中不起重要作用，而螯合笼的结构更为重要。
