MR RECEPTOR IMAGING - ULTRASMALL IRON-OXIDE PARTICLES TARGETED TO ASIALOGLYCOPROTEIN RECEPTORS
MR RECEPTOR IMAGING - ULTRASMALL IRON-OXIDE PARTICLES TARGETED TO ASIALOGLYCOPROTEIN RECEPTORS
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DOI：
10.2214/ajr.155.6.2122660
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发表时间：
1990-12-01
影响因子：
5
通讯作者：
BRADY, TJ
中科院分区：
文献类型：
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作者：
WEISSLEDER, R;REIMER, P;BRADY, TJ
以前，我们已经报道了超小超顺磁性氧化铁（USPIO）颗粒迁移穿过毛细血管内皮，MR受体成像的颗粒药物的设计的先决条件。在目前的研究中，USPIO颗粒通过将阿拉伯半乳聚糖（AG）形式的半乳糖末端偶联到这些颗粒上，特异性地针对脱唾液酸糖蛋白（ASG）受体。生物分布数据显示，ASG导向的AG涂层USPIO（AG-USPIO）颗粒选择性地在肝脏中蓄积，但不在其他器官中蓄积。肝脏的电子显微镜显示电子致密的氧化铁颗粒结合到肝细胞表面膜和大量的细胞内溶酶体。AG-USPIO对去唾液酸糖蛋白受体的特异性通过有和无ASG阻断剂（如D（+）半乳糖和去唾液酸胎球蛋白）的孵育实验得到证实。大鼠体内MR成像显示在低剂量（2 μ mol Fe/kg）下肝脏信号强度显著降低;在脾脏中未观察到显著变化。这种信号强度的降低大于在相同剂量下用常规铁氧化物观察到的信号强度的降低。这些初步的数据表明，第一次，超顺磁性药物可以直接到特定的网站MR成像的策略，如受体靶向。
Previously we have reported that ultrasmall superparamagnetic iron oxide (USPIO) particles migrate across capillary endothelium, a prerequisite for the design of particulate pharmaceuticals for MR receptor imaging. In the current study, USPIO particles are are directed specifically to asialoglycoprotein (ASG) receptors by coupling galactose terminals in the form of arabinogalactan (AG) to these particles. Biodistribution data showed that ASG-directed, AG-coated USPIO (AG-USPIO) particles selectively accumulate in the liver but not in other organs. Electron microscopy of liver showed electron-dense iron oxide particles bound to hepatocyte cell-surface membranes and in large numbers within intracellular lysosomes. The specificity of AG-USPIO for asialoglycoprotein receptors was confirmed by incubation experiments with and without ASG-blocking agents such as D(+)galactose and asialofetuin. In vivo MR imaging in rats showed a significant decrease in liver signal intensity at low doses (2 .mu.mol Fe/kg); no significant changes were observed in the spleen. This decrease in signal intensity is larger than that observed with conventional iron oxides at equal doses. These initial data suggest that, for the first time, superparamagnetic agents can be direct to specific sites for MR imaging by strategies such as receptor targeting.