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.
Highlights
Liver cancer is one of the most common malignant cancers worldwide with an estimated incidence of 782,500 cases in 2012, of which roughly half arose in China [1]
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 near-infrared fluorescence (NIRF) dye have been conjugated
With constant SPIO (250 mg/mL), different supplied amounts of Indocyanine green (ICG) (25–150 μg/mL) yielded a similar absorbance between 780 nm and 830 nm in the UV-vis absorption spectra, which revealed that the probe was suitable for NIRF imaging (Supplementary Figure 2)
Summary
Liver cancer is one of the most common malignant cancers worldwide with an estimated incidence of 782,500 cases in 2012, of which roughly half arose in China [1]. 40 % of patients with liver cancer are diagnosed in the early stage and have a 5-year survival rate of about 28 %. Survival decreases to 10 % and 3 % for patients who are in the regional and distant stages of the disease, respectively [2]. Surgical resection is one of the major therapeutic methods for liver cancer; its 5-year risk of recurrence exceeds 70 % [3], with micro-vascular invasion and micro-residual lesions representing the main risk factors for postoperative recurrence [4]. It is vital for surgeons to realize radical resection to facilitate patient recovery
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