Wu Y Jeffrey, Muldoon Leslie L, Varallyay Csanad, Markwardt Sheila, Jones Richard E, Neuwelt Edward A
Research Service, Veterans Administration Medical Center, Oregon Health and Sciences University, Portland, Oregon 97239, USA.
Am J Physiol Cell Physiol. 2007 Nov;293(5):C1698-708. doi: 10.1152/ajpcell.00215.2007. Epub 2007 Sep 26.
Cellular labeling with ferumoxides (Feridex IV) superparamagnetic iron oxide nanoparticles can be used to monitor cells in vivo by MRI. The objective of this study was to use histology and MRI to evaluate an in vivo, as opposed to in vitro, technique for labeling of mononuclear leukocytes as a means of tracking inflammatory processes in the brain. Long-Evans rats were intravenously injected with 20 mg/kg ferumoxides, ferumoxtran-10, or ferumoxytol with or without protamine sulfate. Leukocytes and splenocytes were evaluated by cell sorting and iron histochemistry or were implanted into the brain for MRI. Injection of ferumoxides/protamine sulfate complex IV resulted in iron labeling of leukocytes (ranging from 7.4 +/- 0.5% to 12.5 +/- 0.9% with average 9.2 +/- 0.8%) compared with ferumoxides (ranging from 3.9 +/- 0.4% to 6.3 +/- 0.5% with average 5.0 +/- 0.5%) or protamine sulfate alone (ranging from 0% to 0.9 +/- 0.7% with average 0.3 +/- 0.3%). Cell sorting analysis indicated that iron-labeled cells were enriched for cell types positive for the myelomonocytic marker (CD11b/c) and the B lymphocyte marker (CD45RA) and depleted in the T cell marker (CD3). Neither ferumoxtran-10 nor ferumoxytol with protamine sulfate labeled leukocytes. In vivo ferumoxides/protamine sulfate-loaded leukocytes and splenocytes were detected by MRI after intracerebral injection. Ferumoxides/protamine complex labeled CD45RA-positive and CD11b/c-positive leukocytes in vivo without immediate toxicity. The dose of feumoxides in this report is much higher than the approved human dose, so additional animal studies are required before this approach could be translated to the clinic. These results might provide useful information for monitoring leukocyte trafficking into the brain.
用超顺磁性氧化铁纳米颗粒（Feridex IV）进行细胞标记可用于通过磁共振成像（MRI）在体内监测细胞。本研究的目的是使用组织学和MRI评估一种用于标记单核白细胞的体内（而非体外）技术，作为追踪脑部炎症过程的一种手段。将20mg/kg的超顺磁性氧化铁、ferumoxtran - 10或ferumoxytol静脉注射给Long - Evans大鼠，注射时有的添加硫酸鱼精蛋白，有的不添加。通过细胞分选和铁组织化学评估白细胞和脾细胞，或将其植入脑部进行MRI检查。与单独使用超顺磁性氧化铁（铁标记范围为3.9±0.4%至6.3±0.5%，平均为5.0±0.5%）或单独使用硫酸鱼精蛋白（铁标记范围为0%至0.9±0.7%，平均为0.3±0.3%）相比，注射超顺磁性氧化铁/硫酸鱼精蛋白复合物IV导致白细胞的铁标记（范围为7.4±0.5%至12.5±0.9%，平均为9.2±0.8%）。细胞分选分析表明，铁标记的细胞富含髓单核细胞标志物（CD11b/c）和B淋巴细胞标志物（CD45RA）呈阳性的细胞类型，而T细胞标志物（CD3）呈阴性。Ferumoxtran - 10和硫酸鱼精蛋白处理的ferumoxytol均未标记白细胞。脑内注射后，通过MRI在体内检测到负载超顺磁性氧化铁/硫酸鱼精蛋白的白细胞和脾细胞。超顺磁性氧化铁/鱼精蛋白复合物在体内标记了CD45RA阳性和CD11b/c阳性的白细胞，且无即刻毒性。本报告中超顺磁性氧化铁的剂量远高于批准的人体剂量，因此在该方法应用于临床之前还需要进行更多的动物研究。这些结果可能为监测白细胞向脑部的迁移提供有用信息。
