Epidermal growth factor receptor-targeted ultra-small superparamagnetic iron oxide particles for magnetic resonance molecular imaging of lung cancer cells in vitro

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. Conclusions We successfully constructed the molecular imaging agent C225-USPIO targeting the EGFR of A549 lung cancer cells. The imaging agent showed good targeting effect and specificity, and reduced MRI T2 value significantly, thus such molecular contrast agents could provide a new way to measure EGFR levels.

Mechanical quality factor of high-overtone bulk acoustic resonator

Mechanical quality factor Qm is a key characteristic parameter of High-overtone bulk acoustic resonator（HBAR）. The effects of structure parameter（thickness） and perfor？mance parameters（characteristic impedance and mechanical attenuation factor） of substrate,piezoelectric film and electrode constituting HBAR on Qm are carried out. The relationships between Qm and these parameters are obtained by a lumped parameter equivalent circuit instead of distributed parameter equivalent circuit near the resonance frequency, and the an？alytical expressions oi Qm are given. The results show that Qm increases non-monotonically with the continuous increase of the substrate thickness for HBAR with certain piezoelectric film thickness, and it approaches to the substrate material mechanical quality factor as the substrate thickness is large. Qm decreases wavily with the continuous increase of the piezoelectric film thickness for HBAR with certain substrate thickness. Sapphire and YAG with low mechanical loss are appropriate as the substrate to get a larger Qm- The electrode loss must be considered since it can reduce Qm- Compared with Au electrode, A1 electrode with lower loss can obtain higher Qm when the appropriate electrode thickness is selected. In addition, Qm decreases with the increase of frequency. These results provide the theoretical basis for optimizing the parameters of HBAR and show that trade-oflFs between Qm and must be considered in the design because their changes are often inconsistent.