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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2016; 22(1): 221-231
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.221
Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma
Jason Wachsmann, Fangyu Peng
Jason Wachsmann, Fangyu Peng, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8542, United States
Fangyu Peng, Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-8542, United States
Fangyu Peng, Harold C Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-8542, United States
Author contributions: Wachsmann J and Peng F analyzed the literature and wrote the manuscript.
Supported by (in part) A faculty research start-up fund to Peng F from the Carman and Ann Adams Foundation, Detroit, Michigan, United States, and Harold C Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Fangyu Peng, MD, PhD, Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8542, United States. fangyu.peng@utsouthwestern.edu
Telephone: +1-214-6452625 Fax: +1-214-6456479
Received: April 29, 2015
Peer-review started: May 12, 2015
First decision: August 25, 2015
Revised: October 18, 2015
Accepted: November 13, 2015
Article in press: November 13, 2015
Published online: January 7, 2016
Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.

Keywords: Hepatocellular carcinoma, Positron emission tomography, Copper metabolism, Radionuclide therapy, RNA interference, Gene therapy

Core tip: Copper is required for cell proliferation and tumor angiogenesis. This article provided an up-to-date review of copper metabolism as a novel theranostic biomarker in hepatocellular carcinoma. Altered copper metabolism is not only a novel biomarker for molecular imaging of extrahepatic metastasis of hepatocellular carcinoma using radioactive copper, but is also a promising target for copper modulation and radionuclide therapy of hepatocellular carcinoma.