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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, and is occurring with greater frequency worldwide. Better methods are needed to detect this disease at an early time point and help guide surgery. A peptide, or protein fragment, has been developed to bind specifically to EpCAM, a molecular target expressed uniquely by cancer cells and to concentrate in tumors. This peptide was labeled with a near-infrared fluorophore, and showed strong binding to HCC cells and in a live animal model using viable human HCC tumors. The peptide was found to be stable in serum, and showed high uptake in HCC tumors with no signs of toxicity. The peptide also bound to cancer that spread throughout the liver and into the lungs, and was more concentrated in tumors than in other organs. These results support the potential usefulness of the EpCAM peptide to detect and remove HCC.

Abstract

Hepatocellular carcinoma (HCC) has emerged as a major contributor to the worldwide cancer burden. Improved methods are needed for early cancer detection and image-guided surgery. Peptides have small dimensions that can overcome delivery challenges to achieve high tumor concentrations and deep penetration. We used phage display methods to biopan against the extra-cellular domain of the purified EpCAM protein, and used IRDye800 as a near-infrared (NIR) fluorophore. The 12-mer sequence HPDMFTRTHSHN was identified, and specific binding to EpCAM was validated with HCC cells in vitro. A binding affinity of kd = 67 nM and onset of k = 0.136 min−1 (7.35 min) were determined. Serum stability was measured with a half-life of T1/2 = 2.6 h. NIR fluorescence images showed peak uptake in vivo by human HCC patient-derived xenograft (PDX) tumors at 1.5 h post-injection. Also, the peptide was able to bind to foci of local and distant metastases in liver and lung. Peptide biodistribution showed high uptake in tumor versus other organs. No signs of acute toxicity were detected during animal necropsy. Immunofluorescence staining of human liver showed specific binding to HCC compared with cirrhosis, adenoma, and normal specimens.

Details

Title
Detection of Hepatocellular Carcinoma in an Orthotopic Patient-Derived Xenograft with an Epithelial Cell Adhesion Molecule-Specific Peptide
Author
Wu, Xiaoli 1 ; Feng, Shuo 1   VIAFID ORCID Logo  ; Tse-Shao, Chang 2   VIAFID ORCID Logo  ; Zhang, Ruoliu 3 ; Jaiswal, Sangeeta 1 ; Choi, Eun-Young K 4 ; Duan, Yuting 5 ; Jiang, Hui 5   VIAFID ORCID Logo  ; Wang, Thomas D 6   VIAFID ORCID Logo 

 Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] (X.W.); [email protected] (S.F.); [email protected] (S.J.) 
 Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] 
 Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] 
 Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] 
 Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] (Y.D.); [email protected] (H.J.) 
 Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] (X.W.); [email protected] (S.F.); [email protected] (S.J.); Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; [email protected]; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] 
First page
2818
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3097834158
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.