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

Background: Hepatocellular carcinoma (HCC) is rising steadily in incidence, and more effective methods are needed for early cancer detection and image-guided surgery. Methods: 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. Results: Binding properties of WKGWSYLWTQQA were characterized by an apparent dissociation constant of k(d) = 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. Conclusions: We have identified a peptide specific for CD44 with properties that are promising for clinical translation to image HCC in vivo.