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.

The theranostic efficiency of tumor-specific, pH-responsive, peptide-modified, liposome-containing paclitaxel and superparamagnetic iron oxide nanoparticles

“…34 Many theranostic liposomes have been reported for therapy and diagnosis, such as topotecanloaded liposome-containing quantum dots (L-QD-TPT) 35 and SPIO NPs coated with liposome-containing indocyanine green modified with a tumor-targeted agent RGD (SPIO@ Liposome-ICG-RGD). 36 In our prepared theranostic PTX/ SPIO-SSL-H 7 K(R 2 ) 2 , PTX was encapsulated in lipid bilayer, SPIO NPs were encapsulated in liposomal aqueous core, and H 7 K(R 2 ) 2 as the targeting molecule was on the liposome surface.…”

Recent developments in multimodality fluorescence imaging probes

“…The imaging results not only suggested the potential use of the dual-modality OFI/MRI probe for imaging of the vulnerable atherosclerotic plaques, but also provided an example in which both fluorescence imaging and active targeting compensate for MRI low sensitivity 65 . Recently, in another report by Chen et al 66 , the dual-modality OFI/MRI was constructed from SPIO nanoparticles coated with functionalized liposomes containing PEG, a tumor-targeted peptide (RGD), and ICG ( Fig. 8 ).…”

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Figure 8 Schematic representation of the synthesis of SPIO@liposome-ICG-RGD (Adapted from Ref. 66 with permission. Copyright©2017 by authors under Creative Commons).

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Value of ultrasound combined with MRI in the diagnosis of primary and recurrent hepatocellular carcinoma

“…Ultrasound (US) and magnetic resonance imaging (MRI) are used to determine the morphological characteristics of liver, judging by the size of the liver and the difference in signal and density between normal and diseased tissue (7,8). US can determine the nature and condition of the lesion by observing the blood perfusion of a liver tumor.…”