Design Strategy for Small Molecule-based Targeted MRI Contrast Agents: Application for Detection of Atherosclerotic Plaques
Design Strategy for Small Molecule-based Targeted MRI Contrast Agents: Application for Detection of Atherosclerotic Plaques
复制标题
基于小分子的靶向 MRI 造影剂的设计策略：在动脉粥样硬化斑块检测中的应用
DOI：
10.1039/c4ob01270d
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发表时间：
2014
影响因子：
3.2
通讯作者：
K.; Nag
中科院分区：
文献类型：
--
作者：
Iwaki;S.; Hokamura;K.; Ogawa;M.; Takehara;Y.; Muramatsu;Y.; Yamane;T.; Hirabayashi;K.; Morimoto;Y.; Hagisawa;K.; Nakahara;K.; Mineno;T.; Terai;T.; Komatsu;T.; Ueno;T.; Tamura;K,; Adachi;Y.; Hirata;Y.; Arita;M.; Arai;H.; Umemura;K.; Nag
钆（III）离子（Gd 3+）络合物被广泛用作磁共振成像（MRI）中的造影剂，并且已经进行了许多尝试以将它们偶联到传感器部分，以便可视化体内感兴趣的生物现象。然而，MRI的低灵敏度使得难以开发用于体内成像的实用MRI造影剂。我们假设可以通过靶向特定的生物环境而不是特定的蛋白质（如受体）来设计实用的MRI造影剂。为了测试这个想法，我们设计并合成了一种基于Gd 3+的MRI造影剂，2BDP3Gd，通过将Gd 3+复合物连接到亲脂性荧光团BODIPY来染色富含脂质的环境，从而可视化动脉粥样硬化斑块。我们发现2BDP 3Gd在细胞水平上选择性地积聚到脂肪细胞的脂滴中。在Watanabe遗传性高脂血症（WHHL）家兔体内静脉注射2BDP 3Gdin后，在T1加权像上可清楚地观察到主动脉粥样硬化斑块。
Gadolinium(III) ion (Gd3+) complexes are widely used as contrast agents in magnetic resonance imaging (MRI), and many attempts have been made to couple them to sensor moieties in order to visualize biological phenomena of interest inside the body. However, the low sensitivity of MRI has made it difficult to develop practical MRI contrast agents for in vivo imaging. We hypothesized that practical MRI contrast agents could be designed by targeting a specific biological environment, rather than a specific protein such as a receptor. To test this idea, we designed and synthesized a Gd3+-based MRI contrast agent, 2BDP3Gd, for visualizing atherosclerotic plaques by linking the Gd3+-complex to the lipophilic fluorophore BODIPY to stain lipid-rich environments. We found that 2BDP3Gd was selectively accumulated into lipid droplets of adipocytes at the cellular level. Atherosclerotic plaques in the aorta of Watanabe heritable hyperlipidemic (WHHL) rabbits were clearly visualized in T1-weighted MR images after intravenous injection of 2BDP3Gdin vivo.