Tumor-targeting peptides functioned as molecular probes are essential for multi-modality imaging and molecular-targeting therapy in caner theronostics. Here, we performed a phage-displayed bio-panning to identify a specific binding peptide targeting Glypican-3 (GPC-3), a promising biomarker in hepatocellular carcinoma (HCC). After screening in the cyclic peptide library, a candidate peptide named F3, was isolated and showed specific binding to HCC cell lines. In a bio-distribution study, higher accumulation of F3 peptide was observed in HepG-2 tumors compared to PC-3 tumors in xenograft models. After labeling with radioactive 68Ga, the F3 peptide tracer enabled the specific detection of tumors in HCC tumor models with PET imaging. More importantly, the expression of GPC-3 in human tissue samples may be distinguished by an F3 fluorescent peptide probe indicating its potential for clinical application. This cyclic peptide targeting GPC-3 has been validated, and may be an alternative to serve as an imaging probe or a targeting domain in the drug conjugate.

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Every year there are nearly 1 million new cases of gastric cancer (GC) reported worldwide, making it the third leading cause of cancerrelated deaths and prompting the World Health Organization to declare it a public health concern. 1 Although the incidence of GC has been substantially declining during the past decades, it remains a high incidence in East Asia. 2 Kita-kyushu lung cancer antigen 1 (KK-LC-1) is a novel tumor target with great therapeutic potential. 3 The KK-LC-1 antigen was originally found in human lung cancer cells but was soon found to be expressed at high levels in breast cancer and GC. [4][5][6] KK-LC-1 is a type of cancer-testis antigen (CTA) that is not be expressed in most normal tissues. Differences between normal and tumor cells are key points of molecular targeted therapy. 7 Small-molecule targeting peptide engineering is a recent area of interest. Compared with antibodies, small-molecule peptides have better tumor permeability, better immunogenicity, and pharmacokinetic parameters. 8 It is worth noting that smallmolecule targeting peptides still have high affinity and selectivity for tumor antigens. These tumor-specific drugs without the structure of immunoglobulins are also called new-generation antibody-like drugs. 9