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

  • J Med Chem. 2021 Nov 11;64(21):15639-15650. doi: 10.1021/acs.jmedchem.1c00697.
Shuo Feng  1 ,  Xiaoqing Meng  1 ,  Zhao Li  2 ,  Tse-Shao Chang  3 ,  Xiaoli Wu  1 ,  Juan Zhou  1 ,  Bishnu Joshi  1 ,  Eun-Young Choi  4 ,  Lili Zhao  5 ,  Jiye Zhu  2 ,  Thomas D Wang  1  3  6
Affiliations
  • 1. Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • 2. Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
  • 3. Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • 4. Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • 5. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • 6. Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
PMID: 34590489 DOI: 10.1021/acs.jmedchem.1c00697
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 ∼24 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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