Theranostic imaging of liver cancer using targeted optical/MRI dual-modal probes

Abstract

The accurate preoperative detection and intraoperative navigation afforded by imaging techniques have had significant impact on the success of liver cancer surgeries. However, it is difficult to achieve satisfactory performance in both diagnosis and surgical treatment processes using any single modality imaging method. Here, we report the synthesis and characteristics of a novel dual-modality magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) probe and verify its feasibility in nude mouse models with liver cancer. The probes are comprised of superparamagnetic iron oxide (SPIO) nanoparticles coated with liposomes to which a tumor-targeted agent, Arg-Gly-Asp peptides (RGD), and a NIRF dye (indocyanine green, ICG) have been conjugated. Specific targeting, biodistribution, and the imaging ability of the probes for MRI-NIRF were examined. Furthermore, we applied the dual-modality methodology toward the preoperative diagnosis and intraoperative guidance of radical resection in mouse models with both orthotopic liver tumors and intrahepatic tumor metastasis. The study demonstrated that both MRI and fluorescent images showed clear tumor delineation after probe injection (SPIO@Liposome-ICG-RGD). The contrast-to-noise ratio obtained from MRI was 31.9 ± 25.4 at post-injection for the preoperative diagnosis, which is helpful for detecting small tumors (0.9 ± 0.5 mm). The maximum tumor to background ratio of NIRF imaging was 2.5 ± 0.3 at 72 h post-injection for effectively capturing miniscule tumor lesions (0.6 ± 0.3 mm) intraoperatively. The novel MRI-NIRF dual modality probes are promising for the achievement of more accurate liver tumor detection and resection.