Potentiometric and relaxometric properties of a gadolinium-based MRI contrast agent for sensing tissue pH
Potentiometric and relaxometric properties of a gadolinium-based MRI contrast agent for sensing tissue pH
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DOI：
10.1021/ic0702926
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发表时间：
2007-06-25
影响因子：
4.6
通讯作者：
Sherry, A. Dean
中科院分区：
文献类型：
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作者：
Kalman, Ferenc K.;Woods, Mark;Sherry, A. Dean
pH敏感造影剂GdDOTA-4AmP（Gd 1）已成功用于通过MRI绘制组织pH。现在进一步的研究表明，根据Gd 3+与配体1混合的pH，可以制备两种不同化学形式的络合物。仅当络合反应在pH 8以上进行时，才获得该络合物的所需pH敏感形式（在此称为II型络合物）作为唯一产物。在较低的pH值下，形成第二络合物，通过与GdDOTA制备过程中形成的中间体类似，我们暂时将其分配给I型络合物，其中Gd 3+仅通过1的附加侧链臂配位。形成的I型络合物的比例主要由络合反应的pH决定。发现Gd 1弛豫率的pH依赖性变化的幅度小于先前报道的（Zhang，S.;吴，K.; Sherry，A. D. Angew.化学成分，Int. Ed. 1999，38，3192），可能是由于早期样品被未知量的I型复合物污染。检查的核磁弛豫分散和弛豫温度曲线，再加上电位滴定的信息，表明膦酸酯侧链的两性特性，使快速质子交换之间的单一结合水的复杂的散装水，从而给Gd 1一个独特的pH值依赖性弛豫，是非常有用的pH值映射的组织通过MRI。
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 Gd3+ 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 Gd3+ 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.