Specific targeting of breast tumor by octreotide-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 3.0-tesla magnetic resonance scanner

Abstract

Targeted magnetic resonance contrast agents have enabled the imaging of biological processes in vivo, and current insights have opened up new perspectives for the monitoring and diagnosis of many diseases. To develop a contrast agent for targeting somatostatin receptors (SSTRs) expressed on breast cancer cells, and to evaluate the detection capabilities of a molecular probe using magnetic resonance (MR) imaging in an in vivo mouse model of breast carcinoma. Octreotide (OCT) was conjugated with polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles by an ethyl-3-(dimethylaminopropyl) carbodiimide (EDC)-mediated reaction. Prussian blue staining for intracellular iron, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cellular MR imaging in vitro were performed on labeled MCF-7 breast cancer cells. Twenty-four mice bearing tumors were divided into two groups: 1) study group with injection of OCT-USPIOs (n=12); 2) control group with injection of USPIOs (n=12). Tumors were monitored in vivo using a 3.0-Tesla MR scanner before and after injection of contrast agents, and the findings were correlated with the histopathological findings. OCT-USPIOs were shown to specifically bind to MCF-7 cells and did not affect proliferation and viability of the cells labeled. T(2) value of the cells labeled with OCT-USPIOs in vitro was 56.465+/-13.147 ms, while those of the cells cultured with USPIOs and gelatin/phosphate-buffered saline (PBS) gel alone were 75.435+/-16.171 ms and 85.950+/-22.352 ms, respectively (P<0.05). Signal intensity of the tumor gradually decreased, and its T(2) value reached a minimum of approximately 24.49% 6 hours after injection of OCT-USPIOs in vivo, compared to a minimum of 21.89% after 2 hours in the control group. Iron depositions were visualized as blue particles in tumor 6 hours after injection of OCT-USPIOs, while no blue particles were observed in the control group. SSTR expression in vitro and in vivo can be selectively and directly imaged with an MR molecular probe. OCT-conjugated PEG-coated USPIO is potentially suitable to be used as a magnetic resonance contrast agent for MR imaging in vivo and increases the sensitivity for the early detection of breast carcinoma.