Novel FGFR4-Targeting Peptide for Single-Photon Emission Computed Tomography Imaging in Hepatocellular Carcinoma

Fibroblast growth factor receptor 4 (FGFR4) is overexpressed in various malignancies, making it a promising target for tumor diagnosis. In this study, we designed a series of FGFR4-targeted peptide-radionuclide conjugates (PRCs) based on a high-affinity peptide ligand derived from the binding epitope of the monoclonal antibody U3-1784. FYQ-8 showed the highest binding affinity for FGFR4-high-expressing HepG2 cells and was selected for radiolabeling with 99mTc via HYNIC, yielding 99mTc-HYNIC-FYQ-8. In xenograft models, this probe demonstrated high uptake (1.89 ± 0.35% ID/g) and produced high-contrast images specifically in high-FGFR4-expressing tumors. These results indicate that 99mTc-HYNIC-FYQ-8 is a promising peptide-based radiotracer for clinical imaging of FGFR4-overexpressing tumors.