Selective targeting of liver cancer with the endothelial marker CD146
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Stefan Thomann1, Thomas Longerich2, Alexandr V. Bazhin1, Walter Mier3, Peter Schemmer1 and Eduard Ryschich1
1 Department of Surgery, University of Heidelberg, Germany
2 Department of Pathology, University of Heidelberg, Germany
3 Department of Nuclear Medicine, University of Heidelberg, Germany
Eduard Ryschich , email:
Keywords: hepatocellular cancer, drug delivery, tumor endothelium
Received: August 07, 2014 Accepted: August 12, 2014 Published: August 13, 2014
Hepatocellular carcinomas are well-vascularized tumors; the endothelial cells in these tumors have a specific phenotype. Our aim was to develop a new approach for tumor-specific drug delivery with monoclonal antibody targeting of endothelial ligands. CD146, a molecule expressed on the endothelial surface of hepatocellular carcinoma, was identified as a promising candidate for targeting. In the present study, endothelial cells immediately captured circulating anti-CD146 (ME-9F1) antibody, while antibody binding in tumors was significantly higher than in hepatic endothelium. Macroscopically, after intravenous injection, there were no differences in the mean accumulation of anti-CD146 antibody in tumor compared to liver tissue , due to a compensating higher blood vessel density in the liver tissue. Additional blockade of nontumoral epitopes and intra-arterial administration, improved selective antibody capture in the tumor microvasculature and largely prevented antibody distribution in the lung and liver. The potential practical use of this approach was demonstrated by imaging of radionuclide-labeled ME-9F1 antibody, which showed excellent tumor-selective uptake. Our results provide a promising principle for the use of endothelial markers for intratumoral drug delivery. Tumor endothelium–based access might offer new opportunities for the imaging and therapy of hepatocellular carcinoma and other liver malignancies.
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