Synthesis and physicochemical characterization of a new gadolinium chelate:: The liver-specific magnetic resonance imaging contrast agent Gd-EOB-DTPA

被引：89

作者：

Schmitt-Willich, H ^{[1
]}

Brehm, M ^{[1
]}

Ewers, CLJ ^{[1
]}

Michl, G ^{[1
]}

Müller-Fahrnow, A ^{[1
]}

Petrov, O ^{[1
]}

Platzek, J ^{[1
]}

Radüchel, B ^{[1
]}

Sülzle, D ^{[1
]}

机构：

[1] Schering AG, Res Labs, D-13342 Berlin, Germany

来源：

INORGANIC CHEMISTRY | 1999年 / 38卷 / 06期

关键词：

D O I：

10.1021/ic981072i

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

A convenient synthesis of disodium S-[4-(4-ethoxybenzyl)-3,6,9-tris[(carboxy-kappa O)methyl]-3,6,9-triazaundecandioato)(5-)-kappa(3)N(3),N-6,N-9,kappa(2)O(1),O-11]gadolinate(2-) (Gd-EOB-DTPA), 1, is reported. This water-soluble complex is presently undergoing phase III clinical trials as a liver-specific contrast agent for magnetic resonance imaging (MRI). The thermodynamic complex stability constant of 1 and the acid dissociation constants of the ligand have been determined as well as the stability constant of the calcium complex Ca-EOB-DTPA (2), which is used as an additive in the pharmaceutical formulation of the contrast agent. The solid-state structure of the ligand S-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6,9-triazaundecanedioic acid (H5EOB-DTPA), 3, has been elucidated in a single crystal X-ray diffraction study. Additionally, HPLC evidence is given that the enantiomerically pure ligand forms two diastereomeric gadolinium complexes in a 65:35 ratio. The kinetics of isomerization of the isolated diastereomers-as dependent on pH and temperature-has been investigated, and thus, the activation energy for the interconversion of these isomers has been estimated to be 75.3 kJ mol(-1). Finally, the structures of the two components of 1 are discussed in terms of four possible diastereomers.

引用

页码：1134 / 1144

页数：11

共 48 条

[1] A novel compound in the lanthanide(III) DOTA series. X-ray crystal and molecular structure of the complex Na[La(DOTA)La(HDOTA)]center dot 10H(2)O [J].