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Synthesis and relaxometric studies of a dendrimer-based pH-responsive MRI contrast agent

机译：基于树枝状聚合物的pH响应MRI造影剂的合成和弛豫研究

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摘要

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 Gd3+ 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.
机译：设计有效的pH响应性MRI造影剂是开发针对肾脏疾病和癌症等疾病的新诊断方法的关键目标。决定药剂有效性的关键因素是“开”状态的松弛度与“关”状态的松弛度之间的差异。在本文中，我们证明可以通过将低分子量试剂与大分子构建体偶联来改善其pH响应作用。报道了其双功能pH响应剂的合成。作为该合成途径的一部分，我们检查了Ing-Manske反应，确定了不良副产物，并建立了促进清洁有效反应的有效条件。双功能pH响应剂与G5-PAMAM树状聚合物的反应产生的产物平均每个树状聚合物为96个螯合物。每个Gd3 +离子，树枝状聚合物共轭物的弛豫度从10.8mM（-1）s（-1）（pH 9）增至24.0 mM（-1）s（-1）（pH 6）。这使我们试剂的弛豫性pH响应Art翻了一番，从最初的低分子量螯合物的51％到树枝状聚合物的122％。

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