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.

The preparation and characteristics of sterically stabilized liposomes containing paclitaxel and super-paramagnetic iron oxide nanoparticles

Theranostics, combining therapy and diagnosis, is an appealing approach for chemotherapy. In the present study, we selected paclitaxel （PTX） as a therapeutic agent, super-paramagnetic iron oxide nanoparticles （SPIO） as a diagnostic agent and sterically stabilized liposomes as a carrier to prepare theranostic liposomes. The SPIO were prepared and characterized. Moreover, the sterically stabilized liposomes containing PTX and SPIO （PTX/SPIO-SSL） were prepared. The characteristics of PTX/SPIO-SSL were investigated. The results indicated that prepared SPIO exhibited super-paramagnetic and could be used for MRI. The average particle size of PTX/SPIO-SSL was about 170 rim, with a polydispersity index （PDI） less than 0.3. The zeta potential of PTX/SPIO-SSL was negative. The PTX entrapment efficiency of PTX/SPIO-SSL was more than 98%. The TEM results indicated the spherical structure and dense SPIO content in PTX/SPIO-SSL. The in vitro release of PTX from PTX/SPIO-SSL and PTX-SSL was almost identical at both pH 6.8 and 7.4. In conclusion, the PTX/SPIO-SSL were prepared and characterized in vitro. The anti-tumor and diagnostic activity of PTX/SPIO-SSL should be investigated deeply in future study.

Lymph node imaging in initial staging of prostate cancer:An overview and update

Accurate nodal staging at the time of diagnosis of prostate cancer is crucial in determining a treatment plan for the patient. Pelvic lymph node dissection is the most reliable method, but is less than perfect and has increased morbidity. Cross sectional imaging with computed tomography (CT) and magnetic resonance imaging (MRI) are non-invasive tools that rely on morphologic characteristics such as shape and size of the lymph nodes. However, lymph nodes harboring metastatic disease may be normal sized and non-metastatic lymph nodes may be enlarged due to reactive hyperplasia. The optimal strategy for preoperative staging remains a topic of ongoing research. Advanced imaging techniques to assess lymph nodes in the setting of prostate cancer utilizing novel MRI contrast agents as well as positron emission tomography (PET) tracers have been developed and continue to be studied. Magnetic resonance lymphography utilizing ultra-small super paramagnetic iron oxide has shown promising results in detection of metastatic lymph nodes. Combining MRL with diffusion-weighted imaging may also improve accuracy. Considerable efforts are being made to develop effective PET radiotracers that are performed using hybrid-imaging systems that combine PET with CT or MRI. PET tracers that will be reviewed in this article include [18F]fluoro-D-glucose, sodium [18F]fluoride, [18F]choline, [11C]choline, prostate specific membrane antigen binding ligands, [11C]acetate, [18F]fluciclovine, gastrin releasing peptide receptor ligands, and androgen binding receptors. This article will review these advanced imaging modalities and ability to detect prostate cancer metastasis to lymph nodes. While more research is needed, these novel techniques to image lymph nodes in the setting of prostate cancer show a promising future in improving initial lymph node staging.