Multi-modal imaging for uptake of peptide ligand specific for CD44 by hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is rising steadily in incidence, and more effective methods are needed for early cancer detection and image-guided surgery. We used a structural model to optimize the peptide sequence. Specific binding was validated in vitro with knockdown, competition, and co-localization assays. Multi-modal imaging was performed to validate specific binding in vivo in orthotopically-implanted human xenograft tumors. Binding properties of WKGWSYLWTQQA were characterized by an apparent dissociation constant of kd = 43 nM, and an apparent association time constant of k = 0.26 min−1. The target-to-background ratio was significantly higher for the target versus control for both modalities. Ex-vivo evaluation using human HCC specimens supported the ability of the peptide to distinguish HCC from other liver pathologies. We have identified a peptide specific for CD44 with properties that are promising for clinical translation to image HCC in vivo.