Magnetic resonance molecular probe for detecting early hepatocellular carcinoma

Abstract

The invention relates to a magnetic resonance molecular probe for detecting early hepatocellular carcinoma. The magnetic resonance molecular probe for detecting the early hepatocellular carcinoma comprises: a ligand of a phosphatidylinositol proteoglycan 3 (GPC3) receptor, wherein the ligand is a biotinylated polypeptide (BT-L5) with an amino acid sequence as shown in SEQ ID NO: 1; an MR imaging developer, wherein the developer is a biotin polyethylene glycol ultra-small superparamagnetic iron oxide (BT-PEG-USPIO) nano composite, wherein the biotinylated polypeptide BT-L5 and the BT-PEG-USPIOare bridged through biotin-avidin to form the magnetic resonance molecular probe of the targeted GPC3. The magnetic resonance molecular probe not only can be combined with a specific receptor expressed by liver cancer cells in a targeting manner, but also has no immunogenicity (or is very low), no toxicity or low toxicity, and can provide enough image signal-to-noise ratio for 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, etal.Glypican-3 Targeting of Liver Cancer Cells Using Multifunctional Nanoparticles.Mol Imaging.2011February ; 10(1):69–77.]....

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 (NSF). )[Kuo PH, Kanal E, Abu-Alfa AK, et al. Gadolinium-BASed MR antagonists 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

However, the combination of BT and SA in this probe is a one-to-one relationship. How to further improve the binding ability of the probe to tumor cells, make tumor cells more clearly visualized, and improve the detection sensitivity have become important bottlenecks in this series of research.

Images