In Vivo Detection of Inflammation Using Pegylated Iron Oxide Particles Targeted at E-Selectin A Multimodal Approach Using MR Imaging and EPR Spectroscopy
In Vivo Detection of Inflammation Using Pegylated Iron Oxide Particles Targeted at E-Selectin A Multimodal Approach Using MR Imaging and EPR Spectroscopy
复制标题
DOI：
10.1097/rli.0b013e3181a49639
复制
发表时间：
2009-07-01
影响因子：
6.7
通讯作者：
Gallez, Bernard
中科院分区：
文献类型：
--
作者：
Radermacher, Kim A.;Beghein, Nelson;Gallez, Bernard
目的：超小颗粒氧化铁 (USPIO) 具有超顺磁性，由于其强大的 T-2 和 T-2* 效应，可用作磁共振成像 (MRI) 中的阴性造影剂。除了这种方法之外，电子顺磁共振（EPR）还提供了量化这些粒子的独特能力。本研究的目的是评估用于非侵入性诊断和炎症监测的分子标记。炎症期间，细胞粘附分子（例如 E-选择素）在内皮细胞表面表达。 E-选择素配体与聚乙二醇化的USPIO颗粒偶联。材料和方法：通过在雄性NMRI小鼠中肌内注射弗氏完全佐剂来诱导炎症。静脉注射移植或未移植的 USPIO 颗粒后，通过 X 波段 EPR 离体定量发炎肌肉中的铁浓度。还通过 L 波段 EPR 以及 T-2 加权 MRI 评估了体内颗粒累积情况。结果：我们确定了注射移植或未移植 UPSIO 颗粒后发炎肌肉中的平均氧化铁浓度，分别为初始注射剂量的 0.8% 和 0.4%。通过 L 波段 EPR，我们观察到发炎肌肉中移植的 USPIO 颗粒的浓度是未移植颗粒的两倍。使用 MRI 实验，与未移植颗粒相比，注射移植颗粒时，在发炎肌肉中明显观察到更高的信号损失。结论：即使考虑到氧化铁的非特异性积累，带有 E-选择素配体的 USPIO 颗粒的靶向也显着提高了检测发炎组织的灵敏度。
Objectives: Ultrasmall particles of iron oxide (USPIO) possess superparamagnetic properties and are used as negative contrast agent in magnetic resonance imaging (MRI) because of their strong T-2 and T-2* effects. Besides this method, electron paramagnetic resonance (EPR) offers the unique capability to quantify these particles. The objective of this study was to evaluate a molecular marker for non invasive diagnosis and monitoring of inflammation. During inflammation cell adhesion molecules such as E-selectin are expressed on the endothelial cell surface. An E-selectin ligand was coupled to pegylated USPIO particles.Materials and Methods: Inflammation was induced by intramuscular injection of Freund's Complete Adjuvant in male NMRI mice. After intravenous injection of grafted or ungrafted USPIO particles, iron concentration in inflamed muscles was quantified ex vivo by X-band EPR. Particle accumulation was also assessed in vivo by L-Band EPR, as well as by T-2-Weighted MRI.Results: We determined the mean iron oxide concentration in inflamed muscles after injection of grafted or ungrafted UPSIO particles, which was 0.8% and 0.4% of the initially injected dose, respectively. By L-band EPR, we observed that the concentration of the grafted USPIO particles in inflamed muscles was twice higher than for the ungrafted particles. Using MRI experiments, a higher signal loss was clearly observed in the inflamed muscle when grafted particles were injected in comparison with the ungrafted particles.Conclusion: Even taking into account a non specific accumulation of iron oxides, the targeting of USPIO particles with E-selectin ligands significantly improved the sensitivity of detection of inflamed tissues.