Kalman Ferenc K, Woods Mark, Caravan Peter, Jurek Paul, Spiller Marga, Tircsó Gyula, Kiraly Róbert, Brücher Ernö, Sherry A Dean
Department of Chemistry, University of Texas at Dallas, P.O. Box 803066, Richardson, Texas 75083, USA.
Inorg Chem. 2007 Jun 25;46(13):5260-70. doi: 10.1021/ic0702926. Epub 2007 Jun 1.
The pH-sensitive contrast agent, GdDOTA-4AmP (Gd1) has been successfully used to map tissue pH by MRI. Further studies now demonstrate that two distinct chemical forms of the complex can be prepared depending upon the pH at which Gd(3+) is mixed with ligand 1. The desired pH-sensitive form of this complex, referred to here as a Type II complex, is obtained as the exclusive product only when the complexation reaction is performed above pH 8. At lower pH values, a second complex is formed that, by analogy with an intermediate formed during the preparation of GdDOTA, we tentatively assign to a Type I complex where the Gd(3+) is coordinated only by the appended side-chain arms of 1. The proportion of Type I complex formed is largely determined by the pH of the complexation reaction. The magnitude of the pH-dependent change in the relaxivity of Gd1 was found to be less than earlier reported (Zhang, S.; Wu, K.; Sherry, A. D. Angew. Chem., Int. Ed. 1999, 38, 3192), likely due to contamination of the earlier sample by an unknown amount of Type I complex. Examination of the nuclear magnetic relaxation dispersion and relaxivity temperature profiles, coupled with information from potentiometric titrations, shows that the amphoteric character of the phosphonate side chains enables rapid prototropic exchange between the single bound water of the complex with the bulk water thereby giving Gd1 a unique pH-dependent relaxivity that is quite useful for the pH mapping of tissues by MRI.
pH 敏感型造影剂 GdDOTA - 4AmP（Gd1）已成功用于通过磁共振成像（MRI）绘制组织 pH 值。进一步的研究表明，根据 Gd(3+)与配体 1 混合时的 pH 值，可以制备出两种不同的化学形式的配合物。只有当络合反应在 pH 8 以上进行时，才能得到这种配合物所需的 pH 敏感形式，这里称为 II 型配合物，且是唯一产物。在较低的 pH 值下，会形成第二种配合物，类似于制备 GdDOTA 过程中形成的中间体，我们暂定其为 I 型配合物，其中 Gd(3+)仅由 1 的附加侧链臂配位。I 型配合物形成的比例很大程度上由络合反应的 pH 值决定。发现 Gd1 的弛豫率随 pH 变化的幅度小于先前报道的值（Zhang, S.; Wu, K.; Sherry, A. D. Angew. Chem., Int. Ed. 1999, 38, 3192），这可能是由于早期样品被未知量的 I 型配合物污染所致。对核磁共振弛豫色散和弛豫率温度曲线的研究，结合电位滴定得到的信息表明，膦酸酯侧链的两性特征使得配合物的单配位水与大量水之间能够快速进行质子转移交换，从而赋予 Gd1 独特的 pH 依赖性弛豫率，这对于通过 MRI 进行组织 pH 映射非常有用。
