Targeted Molecular Imaging of Antigen OC183B2 in Ovarian Cancers Using MR Molecular Probes

Abstract

This study was designed to develop a novel magnetic resonance (MR) probe for the antigen OC183B2 in ovarian cancer cells and investigate its imaging features in vitro and in vivo. Molecular probes were achieved through ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) conjugated to ovarian cancer monoclonal antibodies 183B2 (OCMab183B2) using a chemical method. In the control group, USPIOs were coupled with murine immunoglobulin G (mIgG) and conjugated the same way. Native polyacrylamide gel electrophoresis was used to evaluate the conjugation reaction. The cytotoxicity of the probe was measured using the methyl thiazolyl tetrazolium assay, and its cell-labeling efficiency was evaluated by Prussian blue staining. In vitro cell MR imaging was performed to evaluate the targeting of the probe to the cells. After that, the OCMab183B2 USPIOs and mIgG USPIOs were injected intravenously into nude mice implanted with ovarian cancer xenograft tumors, respectively. T2-weighted imaging and T2 mapping were then performed on a 3.0-T MR imaging system equipped with an animal birdcage coil at different times. Finally, the nude mice were sacrificed for histologic examination to confirm the imaging results. Native polyacrylamide gel electrophoresis displayed an optimal conjugation of USPIOs to OCMab183B2 and mIgG. Various blue-staining particles were found in the cells labeled with the molecular probe at different iron concentrations, and the density of particles was positively related to the iron concentration. Its labeling rate was 96.06%, which was higher than that of USPIOs (62.5%) at the same iron concentration (20 μg/mL). The methyl thiazolyl tetrazolium assay showed that there was no difference in cellular bioactivity between OCMab183B2 USPIO-labeled and nonlabeled cells (P > .05). In vitro cell MR imaging showed that there was an obvious decrease in signal intensity for the probe-labeled cells compared to mIgG USPIO-labeled cells. For in vivo MR imaging, distinct changes of signal intensities and T2 values of ovarian cancers were detected after the injection of OCMab183B2 USPIOs compared to mIgG USPIOs. The histologic analysis showed that iron depositions were visualized in the experimental group but not in the control group. OCMab183B2 USPIO conjugates have the potential to be useful as OC183B2-targeted MR imaging agents for the early detection of ovarian cancers.