Magnetic resonance molecular probe for detecting early-stage hepatocellular carcinoma

Abstract

The present invention relates to a magnetic resonance molecular probe for detecting early-stage hepatocellular carcinoma. The magnetic resonance molecular probe comprises: the ligand of a glypican-3 (GPC3) receptor, wherein the ligand is a biotinylated polypeptide having an amino acid sequence represented by SEQ ID NO:1; and a MR imaging agent, wherein the imaging agent is a streptavidin-polyethylene glycol-ultra-small superparamagnetic iron oxide (SA-PEG-USPIO) nanometer compound, and the biotinylated polypeptide and the SA-PEG-USPIO are combined through biotin-avidin to form the GPC3-targeting magnetic resonance molecular probe. According to the present invention, the magnetic resonance molecular probe can be combined with the specific receptor expressed in hepatocellular carcinoma cells, does not have immunogenicity and toxicity or has low immunogenicity and low toxicity, and can improve the signal-to-noise ratio of the image of the MR imaging.

Description

technical field [0001] The invention relates to a magnetic resonance molecular probe, in particular to a magnetic resonance molecular probe for detecting early hepatocellular carcinoma. Background technique [0002] Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and early diagnosis of HCC is still a key way to improve the prognosis of HCC patients. Clinically, MRI (magnetic resonance imaging) scanning is a common method for diagnosing HCC, but the key to the problem is to improve the accuracy of MRI in diagnosing early HCC. Studies have found that in most HCCs, Glypican-3 (GPC3) protein is overexpressed on the surface of liver cancer cells with high specificity. Animal experiments have shown that monoclonal antibody-mediated MR immunoimaging targeting GPC3 can detect tiny early-stage HCC tumors [James O. Park, et al. Glypican-3 Targeting of Liver Cancer Cells Using Multifunctional Nanoparticles. Mol Imaging. 2011 February;10(1):69–7...

AI Technical Summary

Problems solved by technology

[0008] (1) In terms of ligand selection, antibodies are the most widely used, but the limitations of using monoclonal antibodies as ligands are not only expensive and immunogenic, but more importantly, the high molecular weight of antibodies Can lead to poor tissue penetration and significantly less targeting in in vivo studies

However, the lesions of early hepatocellular carcinoma are relatively small, which may lead to insufficient concentration of local probes and make the MR imaging lesions not clear enough.

[0009] (2) In MR imaging, although gadolinium-containing contrast agents are widely used, gadolinium-containing contrast agents may cause a rare but extremely serious disease - nephrogenic systemic fibrosis (nephrogenic systemic fibrosis, NSF)[Kuo PH, Kanal E, Abu-Alfa AK, et al.Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. Radiology,2007,242(3):647-649]

However, the use of F(ab')2 peptides in PET studies cannot be directly used as magnetic resonance molecular probes for early hepatocellular carcinoma

[0011] (4) The monoclonal antibody and paramagnetic contrast agent Gd3+ currently used are not only immunogenic or toxic to the human body, but also difficult to produce and expensive, which will harm human health and cause low utilization rate

Images