Synthesis and Evaluation of Novel 99mTc-Labeled FGFR2-Targeting Peptides
Synthesis and Evaluation of Novel 99mTc-Labeled FGFR2-Targeting Peptides
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DOI：
10.1021/acs.molpharmaceut.3c00998
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发表时间：
2024-01-03
影响因子：
4.9
通讯作者：
Lu，Jie
中科院分区：
文献类型：
--
作者：
Yao，Jingjing;Fan，Mingxuan;Lu，Jie
To develop radiolabeled FGFR2-targeting probes for visualizing fibroblast growth factor receptor (FGFR) expression levels in the tumor microenvironment, four novel99mTc-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 the99mTc chelating group were designed and synthesized. Thein vitrocellular inhibition, internalization, and efflux results demonstrated that the four99mTc 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 highestin vitrocellular uptake andin vivotumor 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.
