Department of Disaster and Emergency Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Kyushu, Japan.
Magn Reson Imaging. 2010 Jun;28(5):708-15. doi: 10.1016/j.mri.2010.02.003. Epub 2010 Apr 8.
Diagnosis of liver disease has improved because of progress in imaging technology. Among the imaging methods, magnetic resonance imaging (MRI) has the advantage of a lack of radiation exposure, but the basis of the method (imaging of hydrogen atoms in water molecules) makes it hard to detect changes in tissue or the location of the diseased tissue in the liver. The aims of this study are to develop new contrast media for visualization of functional changes in the liver and to check the effectiveness of the media.
We developed a new molecular imaging contrast media that targets the asialoglycoprotein receptor (ASGP-R), a membrane protein that is specific to hepatocytes. We first checked the contrast media diameter and the cytotoxicity. Next, we examined the interaction of the media with ASGP-R through observation of fluorescein isothiocyanate (FITC)-labeled molecular imaging contrast media bound to normal hepatocellular ASGP-R using confocal laser scanning microscopy. Finally, we used MRI to observe hepatocyte interactions with the molecular imaging contrast media.
The contrast media forms a nanoparticle of about 30 nm diameter in aqueous solution and the cytotoxicity is low. In vitro, the media has high specificity for ASGP-R in normal rat hepatocyte RLN-8 cells and this interaction was blocked by lactose (which has a similar molecular structure to that of galactose) and by an anti-ASGP-R antibody. The contrast media markedly enhanced T1-weighted images in MRI of normal rat hepatocytes compared to the signal strength for rat liver cancer cells.
We have shown that our new contrast media for molecular imaging of hepatocytes by MRI is effective in vitro.
由于成像技术的进步，肝脏疾病的诊断得到了改善。在这些成像方法中，磁共振成像（MRI）具有无辐射暴露的优势，但该方法的基础（水分子中氢原子的成像）使得很难检测到组织的变化或肝脏中病变组织的位置。本研究的目的是开发用于可视化肝脏功能变化的新对比剂，并检查该对比剂的有效性。
我们开发了一种新的靶向去唾液酸糖蛋白受体（ASGP-R）的分子成像对比剂，ASGP-R 是一种特异于肝细胞的膜蛋白。我们首先检查了对比剂的直径和细胞毒性。接下来，我们通过共焦激光扫描显微镜观察荧光素异硫氰酸酯（FITC）标记的分子成像对比剂与正常肝细胞 ASGP-R 的结合，检查了该对比剂与 ASGP-R 的相互作用。最后，我们使用 MRI 观察了肝细胞与分子成像对比剂的相互作用。
该对比剂在水溶液中形成约 30nm 直径的纳米颗粒，细胞毒性低。在体外，该对比剂在正常大鼠肝细胞 RLN-8 细胞中对 ASGP-R 具有高特异性，这种相互作用可被乳糖（与半乳糖具有相似的分子结构）和抗 ASGP-R 抗体阻断。与大鼠肝癌细胞相比，该对比剂在正常大鼠肝细胞的 MRI 中显著增强了 T1 加权图像的信号强度。
我们已经证明，我们用于 MRI 肝细胞分子成像的新型对比剂在体外是有效的。
