Synthesis and relaxometric studies of a dendrimer-based pH-responsive MRI contrast agent
Synthesis and relaxometric studies of a dendrimer-based pH-responsive MRI contrast agent
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DOI：
10.1002/chem.200800402
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Sherry, A. Dean
中科院分区：
文献类型：
--
作者：
Ali, M. Meser;Woods, Mark;Sherry, A. Dean
设计有效的pH响应型磁共振成像（MRI）造影剂是开发针对肾病和癌症等疾病的新诊断方法的一个关键目标。决定一种造影剂有效性的一个关键因素是“开启”状态与“关闭”状态的弛豫率之间的差异。在本文中，我们证明通过将一种低分子量造影剂与一种大分子构建体偶联，可以提高其pH响应作用。报道了一种双功能pH响应型造影剂的合成。作为该合成途径的一部分，我们研究了英格 - 曼斯克（Ing - Manske）反应，确定了一种不良副产物，并确定了促进清洁有效反应的有效条件。双功能pH响应型造影剂与G5 - 聚酰胺 - 胺（PAMAM）树枝状大分子反应，得到的产物每个树枝状大分子平均有96个螯合物。树枝状大分子偶联物的弛豫率从每个钆（Gd³⁺）离子在pH为9时的10.8 mM⁻¹s⁻¹升高到pH为6时的24.0 mM⁻¹s⁻¹。这使得我们的造影剂的弛豫率pH响应（Art）从原始低分子量螯合物的仅51%提高到树枝状大分子的122%，增加了一倍多。
The design of effective pH responsive MRI contrast agents is a key goal in the development of new diagnostic methods for conditions Such as kidney disease and cancer. A key factor determining the effectiveness of an agent is the difference between the relaxivity of the "on" state compared to that of the "off" state. In this paper, we demonstrate that it is possible to improve the pH-responsive action of a low molecular weight agent by conjugating it to a macromolecular construct. The synthesis of it bifunctional pH responsive agent is reported. As part of that synthetic pathway we examine the Ing-Manske reaction, identifying an undesirable by-product and establishing effective conditions for promoting a clean and effective reaction. Reaction of the bifunctional pH responsive agent with a G5-PAMAM dendrimer yielded a product with an average of 96 chelates per dendrimer. The relaxivity of the dendrimer conjugate rises from 10.8mM(-1)s(-1) (pH 9) to 24.0 mM(-1)s(-1) (pH 6) per Gd(3+) ion. This more than doubles the relaxivity pH response, Art, of our agent from just 51 % for the original low molecular weight chelate to 122% for the dendrimer.