Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku-Katsura, Kyoto, Japan.
Nanomedicine. 2011 Oct;7(5):638-46. doi: 10.1016/j.nano.2011.01.015. Epub 2011 Feb 17.
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 (Gd(3+)), 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 Gd(3+) 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.
新设计并合成了质子弛豫率比商用 Gd-DOTA 高两倍的 Gd-Me(2)DO2A。Me(2)DO2A 保持了与镓离子（Gd(3+)）的高结合特性，Gd-Me(2)DO2A 被有效地包裹在脱铁铁蛋白空腔内，进一步将 T(1)弛豫率提高了 10 倍，基于 Gd 的弛豫率比 Gd-DOTA 高。高 T(1)弛豫率是通过以下两种方式实现的：(i) 螯合物中水分子与 Gd(3+)离子的可及性增加；(ii) 包裹的大分子效应。通过葡聚糖对脱铁铁蛋白的表面修饰，可以延长脱铁铁蛋白在体内的血液清除时间。荷瘤小鼠的磁共振成像显示，由于增强的渗透和滞留效应，脱铁铁蛋白造影剂作为明亮的信号有效地完成了肿瘤检测。单次剂量毒性试验表明没有严重的副作用。因此，载镓脱铁铁蛋白是一种新型磁共振成像造影剂的候选物。
