Synthesis, characterization, and relaxivity of two linear Gd(DTPA)-polymer conjugates
Synthesis, characterization, and relaxivity of two linear Gd(DTPA)-polymer conjugates
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DOI：
10.1021/bc000065r
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发表时间：
2001-03-01
影响因子：
4.7
通讯作者：
Geraldes, CFGC
中科院分区：
文献类型：
--
作者：
Duarte, MG;Gil, MH;Geraldes, CFGC
合成了两种Gd（DTPA）（2-）的线性聚酰胺缀合物，并通过高分辨核磁共振（NMR）和尺寸排阻色谱（SEC）对其进行了表征。DTPA分别与1，6-己二胺和反式-1，4-环己二胺共聚，得到了低分散性的聚合物DTPA-HMD和DTPA-CHD。它们在溶液中的分子的灵活性进行了研究，使用C-13自旋-晶格弛豫时间测量，表明环己二胺连接部分的DTPA-HMD聚合物是更刚性比DTPA-CHD。采用核磁弛豫分散法研究了连接官能团的柔性对Gd ~（3+）-DTPA-聚合物共轭物弛豫性能的影响。Gd（DTPA-CHD）聚合物的弛豫率仅略高于Gd（DTPA-HMD）聚合物的弛豫率，并且仅比小的Gd-DTPA样螯合物的通常值高两倍。这两种聚合物获得的低弛豫率，远低于预期的聚合物表观分子量，结果从他们的大量剩余的灵活性，也从一个太长的，非最佳的，值的内球水交换率。这些聚合物化合物也很快从大鼠血液中清除，表明它们作为MRA的血池造影剂的价值有限。
Two linear polyamide conjugates of Gd(DTPA)(2-) were synthesized and characterized by high-resolution nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography (SEC). DTPA was copolymerized with two different diamines, 1,6-hexanediamine and trans-1,4-cyclohexanediamine, yielding the polymers DTPA-HMD and DTPA-CHD, with low polydispersity. Their molecular flexibility in solution was studied using C-13 spin-lattice relaxation time measurements, indicating that the cyclohexanediamine linking moiety of the DTPA-HMD polymer is more rigid than that of DTPA-CHD. The influence of the flexibility of the linking functionalities on the relaxivity of the Gd3+-DTPA-polymer conjugates was studied by water nuclear magnetic relaxation dispersion (NMRD). The relaxivity of the Gd(DTPA-CHD) polymer was only slightly higher than that of the Gd(DTPA-HMD) polymer, and only two times higher than the usual values for small Gd-DTPA-like chelates. The low relaxivities obtained for both polymers, much lower than expected from the polymer apparent molecular weights, result from their substantial residual flexibility, and also from a too long, nonoptimal, value of the inner-sphere water exchange rate. These polymeric compounds are also cleared very quickly from the blood of rats, indicating that they are of limited value as blood pool contrast agents for MRA.