Fractionated Feridex and positive contrast: In vivo MR imaging of atherosclerosis
Fractionated Feridex and positive contrast: In vivo MR imaging of atherosclerosis
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DOI：
10.1002/mrm.21541
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发表时间：
2008-04-01
影响因子：
3.3
通讯作者：
Fayad, Zahi A.
中科院分区：
文献类型：
--
作者：
Briley-Saebo, Karen C.;Mani, Venkatesh;Fayad, Zahi A.
巨噬细胞已被确定为动脉粥样硬化发病的关键因素。超小氧化铁颗粒（USPIOs）已被用于被动靶向斑块内巨噬细胞。对于葡聚糖基uspio，巨噬细胞的摄取可能受到颗粒大小的调节。当前研究的目的是测试分离的Feridex对动脉粥样硬化兔子巨噬细胞摄取的功效。Feridex的分离得到了15nm的USPIO，其血液半衰期为15.9 h，肝脏保留率为6.4%。饲喂4.8 mg Fe/kg feidex后，feidex的血液清除率和肝脏滞留率分别为0.46 h和60%。给动脉粥样硬化兔子0.5或4.8 mg /kg剂量的feidex或Feridex分剂。注射后24小时1.5T行MRI检查。Perls和RAM-11染色检测铁沉积。MRI显示，使用常规梯度回波（GRE）序列，在给药分剂Feridex后出现剂量依赖性信号损失。即使在低剂量下，也观察到明显的信号丧失与组织学相关。给药家兔血管壁未见信号衰减和铁沉积。本研究结果表明，优化USPIOs用于斑块内巨噬细胞检测是可能的。
Macrophages have been identified as a critical factor in the pathogenesis of atherosclerosis. Ultrasmall iron oxide particles (USPIOs) have been used to passively target intraplaque macrophages. For dextran-based USPIOs, uptake into macrophages may be modulated by particle size. The aim of the current study was to test the efficacy of fractionated Feridex with respect to macrophage uptake in atherosclerotic rabbits. Fractionation of Feridex resulted in a 15-nm USPIO that exhibited a blood half-life of 15.9 h and liver retention of 6.4%. Blood clearance and liver retention of Feridex was 0.46 h and 60%, following administration of 4.8 mg Fe/kg Feridex. Atherosclerotic rabbits were administered 0.5 or 4.8 mg Fe/kg dosages of either fractionated Feridex or Feridex. MRI was performed at 1.5T over a 24-h time period postinjection. Perls and RAM-11 staining was performed to identify iron deposition. MRI showed a dose-dependent signal loss using conventional gradient echo (GRE) sequences following administration of fractionated Feridex. Even at low dose, significant signal loss was observed that correlated with histology. No signal attenuation or iron deposition was observed in the vessel wall of rabbits administered Feridex. Results of this study suggest that it may be possible to optimize USPIOs for intraplaque macrophage detection.