Background Magnetic resonance (MR) molecular imaging can detect abnormalities associated with disease at the level of cell and molecule. The epidermal growth factor receptor (EGFR) plays an important role in the d...Background Magnetic resonance (MR) molecular imaging can detect abnormalities associated with disease at the level of cell and molecule. The epidermal growth factor receptor (EGFR) plays an important role in the development of lung cancer. This study aimed to explore new MR molecular imaging targeting of the EGFR on lung cancer cells. Methods We attached ultra-small superparamagnetic iron oxide (USPIO) particles to cetuximab (C225) anti-human IgG using the carbodiimide method. We made the molecular MR contrast agents C225-USPIO and IgG-USPIO, the latter as a control reagent, and determined concentrations according to the Fe content. Lung cancer A549 cells were cultured and immunocytochemistry (SP) was used to detect the expression of EGFR on cells. We detected the binding rate of C225-USPIO to A549 cells with immunofluorescence staining and flow cytometry. We cultured A549 cells with C225-USPIO at a Fe concentration of 50 pg/ml and assayed the binding of C225-USPIO after 1 hour with Prussian blue staining and transmission electron microscopy (TEM). We determined the effects on imaging of the contrast agent targeted to cells using a 4.7T MRI. We did scanning on the cells labeled with C225-USPIO, IgG-USPIO, and distilled water, respectively. The scanning sequences included axial T1WI, T2WI. Results Immunocytochemical detection of lung cancer A549 cells found them positive for EGFR expression. Immunofluorescence staining and flow cytometry after cultivation with different concentrations of C225-USPIO showed the binding rate higher than the control. Prussian blue staining and transmission electron microscopy revealed that in the C225-USPIO contrast agent group of cells the particle content of Fe in cytoplasmic vesicles or on surface was more than that in the control group. The 4.7T MR imaging (MRI) scan revealed the T2WI signal in the C225-USPIO group of cells decreased significantly more than in unlabeled cells, but there was no significant difference between the time gradients. Conclusio展开更多
超小超顺磁性氧化铁粒子(Ultrasmall superparamagnetic iron oxid,USPIO)作为MRI阴性显影剂因其较高的空间分辨率及低毒性近年来已逐渐投入临床使用。结合迅猛发展的分子影像学、高分子聚合物技术,各种肿瘤靶向MRI显影剂受到广泛且深...超小超顺磁性氧化铁粒子(Ultrasmall superparamagnetic iron oxid,USPIO)作为MRI阴性显影剂因其较高的空间分辨率及低毒性近年来已逐渐投入临床使用。结合迅猛发展的分子影像学、高分子聚合物技术,各种肿瘤靶向MRI显影剂受到广泛且深入的研究;USPIO结合不同肿瘤特异性的受体在肿瘤的早期诊断及疗效预测、肿瘤干细胞示踪等方面相比传统的钆螯合物MRI显影剂表现出巨大的潜力及优势。展开更多
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 30470525).
文摘Background Magnetic resonance (MR) molecular imaging can detect abnormalities associated with disease at the level of cell and molecule. The epidermal growth factor receptor (EGFR) plays an important role in the development of lung cancer. This study aimed to explore new MR molecular imaging targeting of the EGFR on lung cancer cells. Methods We attached ultra-small superparamagnetic iron oxide (USPIO) particles to cetuximab (C225) anti-human IgG using the carbodiimide method. We made the molecular MR contrast agents C225-USPIO and IgG-USPIO, the latter as a control reagent, and determined concentrations according to the Fe content. Lung cancer A549 cells were cultured and immunocytochemistry (SP) was used to detect the expression of EGFR on cells. We detected the binding rate of C225-USPIO to A549 cells with immunofluorescence staining and flow cytometry. We cultured A549 cells with C225-USPIO at a Fe concentration of 50 pg/ml and assayed the binding of C225-USPIO after 1 hour with Prussian blue staining and transmission electron microscopy (TEM). We determined the effects on imaging of the contrast agent targeted to cells using a 4.7T MRI. We did scanning on the cells labeled with C225-USPIO, IgG-USPIO, and distilled water, respectively. The scanning sequences included axial T1WI, T2WI. Results Immunocytochemical detection of lung cancer A549 cells found them positive for EGFR expression. Immunofluorescence staining and flow cytometry after cultivation with different concentrations of C225-USPIO showed the binding rate higher than the control. Prussian blue staining and transmission electron microscopy revealed that in the C225-USPIO contrast agent group of cells the particle content of Fe in cytoplasmic vesicles or on surface was more than that in the control group. The 4.7T MR imaging (MRI) scan revealed the T2WI signal in the C225-USPIO group of cells decreased significantly more than in unlabeled cells, but there was no significant difference between the time gradients. Conclusio
文摘超小超顺磁性氧化铁粒子(Ultrasmall superparamagnetic iron oxid,USPIO)作为MRI阴性显影剂因其较高的空间分辨率及低毒性近年来已逐渐投入临床使用。结合迅猛发展的分子影像学、高分子聚合物技术,各种肿瘤靶向MRI显影剂受到广泛且深入的研究;USPIO结合不同肿瘤特异性的受体在肿瘤的早期诊断及疗效预测、肿瘤干细胞示踪等方面相比传统的钆螯合物MRI显影剂表现出巨大的潜力及优势。