Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2015; 21(14): 4275-4283
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4275
Preparation of magnetic resonance probes using one-pot method for detection of hepatocellular carcinoma
You-Wei Li, Zheng-Guang Chen, Zhou-She Zhao, Hong-Li Li, Ji-Chen Wang, Zong-Ming Zhang
You-Wei Li, Department of Radiology, Beijing Chuiyangliu Hospital Affiliated to School of Medicine, Tsinghua University, Beijing 100022, China
Zheng-Guang Chen, Department of Radiology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
Zhou-She Zhao, Hong-Li Li, GE Healthcare China, Beijing Economic and Technology Development Area, Beijing 100176, China
Ji-Chen Wang, Department of Radiology, Nanjing BenQ Hospital, Nanjing 210036, Jiangsu Province, China
Zong-Ming Zhang, Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing 100073, China
Author contributions: Zhang ZM and Zhao ZS designed the study; Li YW, Chen ZG and Li HL performed the study; Wang JC provided analytic tools and analyzed the data; Li YW and Chen ZG wrote the paper.
Supported by National Natural Science Foundation of China, No. 81071996.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Zong-Ming Zhang, MD, PhD, Professor, Director, Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, No. 1 Taipingqiaoxili, Fengtai District, Beijing 100073, China. zhangzongming@mail.tsinghua.edu.cn
Telephone: +86-10-63503046 Fax: +86-10-63465865
Received: August 20, 2014
Peer-review started: August 20, 2014
First decision: November 4, 2014
Revised: November 17, 2014
Accepted: December 5, 2014
Article in press: December 8, 2014
Published online: April 14, 2015
Abstract

AIM: To prepare the specific magnetic resonance (MR) probes for detection of hepatocellular carcinoma (HCC) using one-pot method.

METHODS: The carboxylated dextran-coated nanoparticles were conjugated with anti-α-fetoprotein (anti-AFP) or anti-glypican 3 (anti-GPC3) antibodies through 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS)-mediated reaction to synthesize the probes. The physical and chemical properties of the probes were determined by transmission electron microscopy (TEM) and dynamic light scattering, and the relaxivity was compared to uncombined ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) using a 1.5T clinical MR scanner. The binding efficiency of the antibodies to nanoparticles was measured with an ultraviolet-visible spectrophotometer. In addition, the probes were incubated with targetable cells in vitro.

RESULTS: The superparamagnetic MR probes (anti-GPC3-USPION probe and anti-AFP-USPION probe) were synthesized using one-pot method. Their mean hydrodynamic diameter was 47 nm with a broader slight size distribution. The coupling efficiency of carboxylated dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) with anti-GPC3 or anti-AFP antibody was 15.9% and 88.8%, respectively. Each of the USPIO nanoparticles may bind 3 GPC3 antibodies or 12 AFP antibodies. The statistical analysis showed no significance (P > 0.05) in shortening the T1 and T2 values when comparing the USPIO-AFP or USPIO-GPC3 to USPIO. Analysis of TEM images revealed that anti-GPC3-USPION probes and anti-AFP-USPION probes could specifically enter into the HepG2 cell by combining with the GPC3 receptors or AFP receptors, whereas the HepG2 cell sample incubated with USPIONs showed no or few nanoparticles in the cytoplasm.

CONCLUSION: The synthesized probes using one-pot method can be used for in vitro experimental study and have potential clinical application in MR imaging for detection of hepatocellular carcinomas.

Keywords: Hepatocellular carcinoma, Ultrasmall superparamagnetic iron oxide nanoparticles, Specific probe, One-pot method, Magnetic resonance imaging

Core tip: The preparation process of magnetic resonance probes should be as simple as possible in order to have mass production. We developed a method named one-pot method by modifying the traditional methods to prepare an anti-glypican 3-ultrasmall superparamagnetic iron oxide nanoparticle (USPION) probe and an anti-α-fetoprotein-USPION probe and determined their physical and chemical properties and bioactivity. The results showed that this method is simple and convenient to synthesize the magnetic resonance molecular probes. The synthesized probes entered into the specific cells in vitro.