Synthesis and Evaluation of Novel 99mTc-Labeled FGFR2-Targeting Peptides

To develop radiolabeled FGFR2-targeting probes for visualizing fibroblast growth factor receptor (FGFR) expression levels in the tumor microenvironment, four novel ^99mTc-labeled FGFR2-targeting peptides ([^99mTc]Tc-FGFR2-1, [^99mTc]Tc-FGFR2-2, [^99mTc]Tc-FGFR2-3, and [^99mTc]Tc-FGFR2-4) with different amino acid linkers between the targeted peptide moiety and the ^99mTc chelating group were designed and synthesized. The in vitro cellular inhibition, internalization, and efflux results demonstrated that the four ^99mTc complexes exhibited FGFR2-specific binding and prolonged cellular retention in DU145 human prostate cancer cells, which indicated that modification from the glycine side (N-terminal) of CH02 was feasible. Among them, [^99mTc]Tc-FGFR2-1 exhibited the highest in vitro cellular uptake and in vivo tumor uptake at 30 min postinjection, and tumor uptake could be significantly inhibited by the competitor CH02 (53% inhibited, p < 0.05), suggesting the tumor-specific targeting ability of [^99mTc]Tc-FGFR2-1. The DU145-xenografted tumor lesions were clearly visualized by single photon emission computed tomography (SPECT)/CT at 30 min postinjection of [^99mTc]Tc-FGFR2-1, highlighting its potential as a SPECT imaging probe for tumor FGFR2 detection.