McConnell Heather L, Schwartz Daniel L, Richardson Brian E, Woltjer Randall L, Muldoon Leslie L, Neuwelt Edward A
Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, USA.
Nanomedicine. 2016 Aug;12(6):1535-42. doi: 10.1016/j.nano.2016.03.009. Epub 2016 Apr 9.
Ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles can enhance contrast between neuroinflamed and normal-appearing brain tissue when used as a contrast agent for high-sensitivity magnetic resonance imaging (MRI). Here we used an anti-dextran antibody (Dx1) that binds the nanoparticle's carboxymethyldextran coating to differentiate ferumoxytol from endogenous iron and localize it unequivocally in brain tissue. Intravenous injection of ferumoxytol into immune-competent rats that harbored human tumor xenograft-induced inflammatory brain lesions resulted in heterogeneous and lesion-specific signal enhancement on MRI scans in vivo. We used Dx1 immunolocalization and electron microscopy to identify ferumoxytol in affected tissue post-MRI. We found that ferumoxytol nanoparticles were taken up by astrocyte endfeet surrounding cerebral vessels, astrocyte processes, and CD163(+)/CD68(+) macrophages, but not by tumor cells. These results provide a biological basis for the delayed imaging changes seen with ferumoxytol and indicate that ferumoxytol-MRI can be used to assess the inflammatory component of brain lesions in the clinic.
当作为高灵敏度磁共振成像（MRI）的造影剂使用时，多聚麦芽糖超小超顺磁性氧化铁纳米颗粒可增强神经炎症组织与外观正常的脑组织之间的对比度。在此，我们使用了一种抗葡聚糖抗体（Dx1），它能与纳米颗粒的羧甲基葡聚糖涂层结合，从而将多聚麦芽糖与内源性铁区分开来，并明确其在脑组织中的定位。将多聚麦芽糖静脉注射到携带人肿瘤异种移植诱导的炎症性脑损伤的免疫健全大鼠体内，导致体内MRI扫描出现异质性且病变特异性的信号增强。我们使用Dx1免疫定位和电子显微镜在MRI后识别受影响组织中的多聚麦芽糖。我们发现，多聚麦芽糖纳米颗粒被脑血管周围的星形胶质细胞终足、星形胶质细胞突起和CD163(+)/CD68(+)巨噬细胞摄取，但未被肿瘤细胞摄取。这些结果为多聚麦芽糖所见的延迟成像变化提供了生物学基础，并表明多聚麦芽糖-MRI可用于临床评估脑损伤的炎症成分。
