Sherry A D, Cacheris W P, Kuan K T
University of Texas, Dallas, Richardson 75083-0688.
Magn Reson Med. 1988 Oct;8(2):180-90. doi: 10.1002/mrm.1910080208.
Five DTPA-amide and ester derivatives have been synthesized and their Gd3+ stability constants have been measured using a simple spectrophotometric method. These results are compared to stability constants measured for Gd3+ binding to two different DTPA-conjugated proteins. Although the thermodynamic constants for Gd3+ binding to DTPA-monopropylamide and DTPA-monopropylester relative to Gd(DTPA)2- decrease by log K = 2.6 and 3.4, respectively, the blood pH conditional constants differ from Gd(DTPA)2- only by log K = 1.2 and 1.9, respectively. The corresponding dipropylamide and ester conjugates of DTPA show considerably lower thermodynamic and conditional constants. This has important implications in the covalent attachment of chelates to macromolecules for use in magnetic resonance imaging. The measured binding constants for Gd(DTPA)-IgG and Gd(DTPA)-BSA suggest that many of the DTPA molecules in these systems, prepared under our experimental conditions, are disconjugated. The model compound results indicate that it is important to use methods in attaching DTPA to macromolecules which preclude dionjugation of the chelate. Otherwise, their affinity for Gd3+ and consequently their usefulness as MRI contrast agents may be severely compromised.
已合成了五种二乙三胺五乙酸（DTPA）-酰胺和酯衍生物，并使用一种简单的分光光度法测量了它们的钆（Gd3+）稳定性常数。将这些结果与测量的Gd3+与两种不同的DTPA共轭蛋白结合的稳定性常数进行比较。尽管相对于Gd（DTPA）2-，Gd3+与DTPA-单丙酰胺和DTPA-单丙酯结合的热力学常数分别降低了log K = 2.6和3.4，但血液pH条件常数与Gd（DTPA）2-的差异仅分别为log K = 1.2和1.9。DTPA相应的二丙酰胺和酯共轭物显示出明显更低的热力学和条件常数。这对于螯合物与大分子的共价连接用于磁共振成像具有重要意义。测量的Gd（DTPA）-免疫球蛋白（IgG）和Gd（DTPA）-牛血清白蛋白（BSA）的结合常数表明，在我们的实验条件下制备的这些系统中的许多DTPA分子是解离的。模型化合物的结果表明，使用防止螯合物解离的方法将DTPA连接到大分子上很重要。否则，它们对Gd3+的亲和力以及因此作为磁共振成像造影剂的效用可能会受到严重影响。
