Effective encapsulation of a new cationic gadolinium chelate into apoferritin and its evaluation as an MRI contrast agent
Effective encapsulation of a new cationic gadolinium chelate into apoferritin and its evaluation as an MRI contrast agent
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DOI：
10.1016/j.nano.2011.01.015
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发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Kimura, Shunsaku
中科院分区：
文献类型：
--
作者：
Makino, Akira;Harada, Hiroshi;Kimura, Shunsaku
新设计合成了T-1质子弛豫度是商品化Gd-DOTA的两倍的Gd-Me(2)DO2A。Me(2)DO2A保持了与Gd~(3+)的高缔合性质，Gd-Me(2)DO2A被有效地包裹到载铁蛋白空腔中，进一步提高了T-1弛豫度，以Gd为基准，比Gd-DOTA高10倍。高的T-1弛豫度是由于(I)螯合物中水分子对Gd3+离子的可及性增加和(Ii)包埋的大分子效应所致。通过用葡聚糖对载脂蛋白进行表面修饰，可以延长载脂蛋白在体内的清除时间。荷瘤小鼠的磁共振成像显示，载脂蛋白造影剂作为一种明亮的信号，由于其增强的渗透和滞留效应，有效地完成了肿瘤的检测。单次给药毒性试验未见严重副作用。因此，载脂蛋白包裹的Gd可能是一种新的磁共振成像造影剂的候选者。来自临床编辑：在Makino等人的这项研究中，一种新的阳离子Gd螯合物与载脂蛋白的包裹方法导致了比标准临床使用的Gd对比剂高10倍的质子弛豫度。如果这种复合体通过毒性研究，它将具有巨大的临床意义，它将提供一种更灵敏的方法来可视化血脑屏障的分解。(C)2011 Elsevier Inc.保留所有权利。
Gd-Me(2)DO2A with a T-1 proton relaxivity twice as high as that of commercial Gd-DOTA was newly designed and synthesized. Me(2)DO2A kept its high association property with gadolinium ions (Gd3+), and the Gd-Me(2)DO2A was efficiently encapsulated into the apoferritin cavity to further enhance the T-1 relaxivity as much as 10-fold higher than Gd-DOTA on a Gd basis. The high T-1 relaxivity was attained by (i) increased accessibility of water molecules to Gd3+ ions in the chelate and (ii) macromolecular effect of the encapsulation. By the surface modification of apoferritin with dextran, in vivo blood clearance time of apoferritin could be prolonged. Magnetic resonance imaging of tumor-bearing mice showed that the apoferritin contrast agent accomplished tumor detection effectively as a bright signal as a result of the enhanced permeation and retention effect. Single-dose toxicity test showed no serious side effects. The apoferritin-encapsulated Gd is therefore a possible candidate for a new magnetic resonance imaging contrast agent.From the Clinical Editor: In this study by Makino et al, a novel encapsulation method of a cationic Gd chelate with apoferritin led to a proton relaxivity 10 times higher than that of standard clinically used Gd contrast dyes. If this complex passed toxicity studies, it would have an enormous clinical significance in providing a much more sensitive method to visualize BBB breakdown. (C) 2011 Elsevier Inc. All rights reserved.