Boros Eszter, Karimi Shima, Kenton Nathaniel, Helm Lothar, Caravan Peter
The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , 149 Thirteenth Street, Suite 2301, Charlestown, Massachusetts 02129, United States.
Inorg Chem. 2014 Jul 7;53(13):6985-94. doi: 10.1021/ic5008928. Epub 2014 Jun 12.
Here, we describe the synthesis of the single amino acid chelator DOTAlaP and four of its derivatives. The corresponding gadolinium(III) complexes were investigated for their kinetic inertness, relaxometric properties at a range of fields and temperatures, water exchange rate, and interaction with human serum albumin (HSA). Derivatives with one inner-sphere water (q = 1) were determined to have a mean water residency time between 8 and 6 ns in phoshate-buffered saline at 37 °C. The corresponding europium complexes were also formed and used to obtain information on the hydration number of the corresponding coordination complexes. Two complexes capable of binding HSA were also synthesized, of which one, Gd(5b), contains no inner-sphere water, while the other derivative, Gd(4b), is a mixture of ca. 15% q =1 and 85% q = 0. In the presence of HSA, the latter displayed a very short mean water residency time (τM(310) = 2.4 ns) and enhanced relaxivity at intermediate and high fields. The kinetic inertness of Gd(4b) with respect to complex dissociation was decreased compared to its DOTAla analogue but still 100-fold more inert than Gd(BOPTA)(H2O). Magnetic resonance imaging in mice showed that Gd(4b) was able to provide 38% better vessel to muscle contrast compared to the clinically used HSA binding agent MS-325.
在此，我们描述了单氨基酸螯合剂DOTAlaP及其四种衍生物的合成。研究了相应的钆（III）配合物的动力学惰性、在一系列场强和温度下的弛豫特性、水交换速率以及与人血清白蛋白（HSA）的相互作用。在37℃的磷酸盐缓冲盐水中，具有一个内球水（q = 1）的衍生物的平均水停留时间在8到6纳秒之间。还形成了相应的铕配合物，并用于获取有关相应配位配合物水合数的信息。还合成了两种能够结合HSA的配合物，其中一种，Gd(5b)，不含内球水，而另一种衍生物，Gd(4b)，是约15% q = 1和85% q = 0的混合物。在HSA存在下，后者表现出非常短的平均水停留时间（τM(310) = 2.4纳秒），并且在中场和高场下弛豫率增强。与DOTAla类似物相比，Gd(4b)在配合物解离方面的动力学惰性有所降低，但仍比Gd(BOPTA)(H2O)惰性高100倍。小鼠体内的磁共振成像显示，与临床使用的HSA结合剂MS-325相比，Gd(4b)能够提供38%更好的血管与肌肉对比度。
