Department of Applied Chemistry, Kyungpook National University, Buk-gu, Daegu, Republic of Korea.
J Med Chem. 2011 Jan 13;54(1):143-52. doi: 10.1021/jm100966t. Epub 2010 Dec 9.
Gd-complexes of the type [Gd(L)(H(2)O)]·xH(2)O (5a-c), where L is DOTA conjugates of tranexamic acid (4a) and tranexamic esters (4b,c), have been prepared as a new class of MRI blood-pool contrast agents (BPCAs). Thermodynamic stability (K(GdL)) and pharmacokinetic inertness of 5 compare well with or better than those of analogous MRI contrasting agents (CAs) such as Gd-DOTA and Gd-DTPA-BMA. Their R(1)-relaxivities are significantly higher than those of any of the clinically used MRI CAs. T(1)-weighted MR images of mice administered by 5c demonstrate high blood-pool effect with simultaneous contrast enhancement in liver. The structural uniqueness of 5c lies in the fact that it adopts macrocyclic DOTA instead of acyclic DTPA. In addition, 5c is nonionic and makes no resort to aromatic substituent(s) in the chelate backbone for the blood-pool enhancement. The nature of hepatobiliary uptake demonstrated by 5c may be explained in terms of lipophilicity of tranexamate in the chelate (4c). The cell cytotoxicity test shows no toxicity found with 5, suggesting their use as a practical MRI BPCAs.
[Gd(L)(H2O)]·xH2O（5a-c）型 Gd 配合物，其中 L 是氨甲环酸（4a）和氨甲环酸酯（4b，c）的 DOTA 缀合物，已被制备为一类新型的 MRI 血池对比剂（BPCA）。5 的热力学稳定性（K（GdL））和药代动力学惰性与类似的 MRI 对比剂（CA）如 Gd-DOTA 和 Gd-DTPA-BMA 相当或更好。它们的 R1 弛豫率明显高于任何临床使用的 MRI CA。给予 5c 的小鼠的 T1 加权磁共振图像显示具有高血池效应的同时增强肝脏对比度。5c 的结构独特性在于它采用大环 DOTA 而不是非环状 DTPA。此外，5c 是非离子的，并且在螯合骨架中不依赖于芳基取代基用于血池增强。5c 显示的肝胆摄取性质可以根据螯合物（4c）中氨甲环酸的亲脂性来解释。细胞毒性试验表明 5 没有毒性，表明它们可用作实际的 MRI BPCA。
