Multi-Modal Imaging Probe for Glypican-3 Overexpressed in Orthotopic Hepatocellular Carcinoma.
Shuo FengXiaoqing MengZhao LiTse-Shao ChangXiaoli WuJuan ZhouBishnu JoshiEun-Young ChoiLili ZhaoJiye ZhuThomas D WangPublished in: Journal of medicinal chemistry (2021)
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.
Keyphrases
- amino acid
- early stage
- cell surface
- clinical trial
- deep learning
- convolutional neural network
- optical coherence tomography
- high resolution
- risk factors
- coronary artery bypass
- randomized controlled trial
- single molecule
- fluorescence imaging
- radiation therapy
- living cells
- transcription factor
- structural basis
- coronary artery disease
- machine learning
- binding protein
- lymph node
- neoadjuvant chemotherapy
- sensitive detection
- phase iii
- positron emission tomography