Multi-Modal Imaging Probe for Glypican-3 Overexpressed in Orthotopic Hepatocellular Carcinoma

Shuo Feng; Xiaoqing Meng; Zhao Li; Tse Shao Chang; Xiaoli Wu; Juan Zhou; Bishnu Joshi; Eun Young Choi; Lili Zhao; Jiye Zhu; Thomas D. Wang

doi:10.1021/acs.jmedchem.1c00697

Multi-Modal Imaging Probe for Glypican-3 Overexpressed in Orthotopic Hepatocellular Carcinoma

Shuo Feng, Xiaoqing Meng, Zhao Li, Tse Shao Chang, Xiaoli Wu, Juan Zhou, Bishnu Joshi, Eun Young Choi, Lili Zhao, Jiye Zhu^*, Thomas D. Wang^*

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) is rising steadily in incidence, and more effective methods are needed for early detection and image-guided surgery. Glypican-3 (GPC3) is a cell surface biomarker that is overexpressed in early-stage cancer but not in cirrhosis. An IRDye800-labeled 12-mer amino acid sequence was identified, and specific binding to GPC3 was validated in vitro and in orthotopically implanted HCC tumors in vivo. Over 4-fold greater binding affinity and 2-fold faster kinetics were measured by comparison with previous GPC3 peptides. Photoacoustic images showed peak tumor uptake at 1.5 h post-injection and clearance within μ24 h. Laparoscopic and whole-body fluorescence images showed strong intensity from tumor versus adjacent liver with about a 2-fold increase. Immunofluorescence staining of human liver specimens demonstrated specific binding to HCC versus cirrhosis with 79% sensitivity and 79% specificity, and normal liver with 81% sensitivity and 84% specificity. The near-infrared peptide is promising for early HCC detection in clinical trials.

Original language	English (US)
Pages (from-to)	15639-15650
Number of pages	12
Journal	Journal of Medicinal Chemistry
Volume	64
Issue number	21
DOIs	https://doi.org/10.1021/acs.jmedchem.1c00697
State	Published - Nov 11 2021

Funding

This study was funded in part by the National Institutes of Health (U01 CA230669) (T.D.W.) and the UMHS-PUHSC Joint Institute (J.Z., T.D.W.).

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acs.jmedchem.1c00697

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title = "Multi-Modal Imaging Probe for Glypican-3 Overexpressed in Orthotopic Hepatocellular Carcinoma",

abstract = "Hepatocellular carcinoma (HCC) is rising steadily in incidence, and more effective methods are needed for early detection and image-guided surgery. Glypican-3 (GPC3) is a cell surface biomarker that is overexpressed in early-stage cancer but not in cirrhosis. An IRDye800-labeled 12-mer amino acid sequence was identified, and specific binding to GPC3 was validated in vitro and in orthotopically implanted HCC tumors in vivo. Over 4-fold greater binding affinity and 2-fold faster kinetics were measured by comparison with previous GPC3 peptides. Photoacoustic images showed peak tumor uptake at 1.5 h post-injection and clearance within μ24 h. Laparoscopic and whole-body fluorescence images showed strong intensity from tumor versus adjacent liver with about a 2-fold increase. Immunofluorescence staining of human liver specimens demonstrated specific binding to HCC versus cirrhosis with 79% sensitivity and 79% specificity, and normal liver with 81% sensitivity and 84% specificity. The near-infrared peptide is promising for early HCC detection in clinical trials.",

author = "Shuo Feng and Xiaoqing Meng and Zhao Li and Chang, {Tse Shao} and Xiaoli Wu and Juan Zhou and Bishnu Joshi and Choi, {Eun Young} and Lili Zhao and Jiye Zhu and Wang, {Thomas D.}",

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doi = "10.1021/acs.jmedchem.1c00697",

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AU - Feng, Shuo

AU - Meng, Xiaoqing

AU - Li, Zhao

AU - Chang, Tse Shao

AU - Wu, Xiaoli

AU - Zhou, Juan

AU - Joshi, Bishnu

AU - Choi, Eun Young

AU - Zhao, Lili

AU - Zhu, Jiye

AU - Wang, Thomas D.

PY - 2021/11/11

Y1 - 2021/11/11

N2 - Hepatocellular carcinoma (HCC) is rising steadily in incidence, and more effective methods are needed for early detection and image-guided surgery. Glypican-3 (GPC3) is a cell surface biomarker that is overexpressed in early-stage cancer but not in cirrhosis. An IRDye800-labeled 12-mer amino acid sequence was identified, and specific binding to GPC3 was validated in vitro and in orthotopically implanted HCC tumors in vivo. Over 4-fold greater binding affinity and 2-fold faster kinetics were measured by comparison with previous GPC3 peptides. Photoacoustic images showed peak tumor uptake at 1.5 h post-injection and clearance within μ24 h. Laparoscopic and whole-body fluorescence images showed strong intensity from tumor versus adjacent liver with about a 2-fold increase. Immunofluorescence staining of human liver specimens demonstrated specific binding to HCC versus cirrhosis with 79% sensitivity and 79% specificity, and normal liver with 81% sensitivity and 84% specificity. The near-infrared peptide is promising for early HCC detection in clinical trials.

AB - Hepatocellular carcinoma (HCC) is rising steadily in incidence, and more effective methods are needed for early detection and image-guided surgery. Glypican-3 (GPC3) is a cell surface biomarker that is overexpressed in early-stage cancer but not in cirrhosis. An IRDye800-labeled 12-mer amino acid sequence was identified, and specific binding to GPC3 was validated in vitro and in orthotopically implanted HCC tumors in vivo. Over 4-fold greater binding affinity and 2-fold faster kinetics were measured by comparison with previous GPC3 peptides. Photoacoustic images showed peak tumor uptake at 1.5 h post-injection and clearance within μ24 h. Laparoscopic and whole-body fluorescence images showed strong intensity from tumor versus adjacent liver with about a 2-fold increase. Immunofluorescence staining of human liver specimens demonstrated specific binding to HCC versus cirrhosis with 79% sensitivity and 79% specificity, and normal liver with 81% sensitivity and 84% specificity. The near-infrared peptide is promising for early HCC detection in clinical trials.

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Multi-Modal Imaging Probe for Glypican-3 Overexpressed in Orthotopic Hepatocellular Carcinoma

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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