Perfluoro-tert-butyl Group-Derived Capmatinib: Synthesis, Biological Evaluation and Its Application in F-19 Magnetic Resonance Imaging

Capmatinib is an FDA-approved drug to treat metastatic non-small cell lung cancer with MET-exon 14 skipping. Herein, the perfluoro-tert-butyl group, which possesses nine chemically identical fluorine atoms, was introduced on Capmatinib to afford a targeted F-19 magnetic resonance imaging (MRI) probe, perfluoro-tert-butyl group-derived Capmatinib (9F-CAP). The F-19 MRI concentration limit was found to be 25 mM in FLASH sequence. Molecular docking simulation, surface plasmon resonance (SPR) (with a K-d of 40.7 & mu;M), half-inhibitory concentration (with a IC50 of 168 nM), Annexin V, and cytotoxicity assays jointly demonstrated that the 9F-CAP targeted cMET protein specifically. Therefore, the targeted imaging capability of 9F-CAP is of great significance for the preoperative diagnosis of specific cancers.

Automated summary

Capmatinib is an FDA-approved drug for metastatic non-small cell lung cancer with MET-exon 14 skipping. By introducing a perfluoro-tert-butyl group with nine chemically identical fluorine atoms on Capmatinib, a targeted F-19 magnetic resonance imaging (MRI) probe called perfluoro-tert-butyl group-derived Capmatinib (9F-CAP) was developed. The study demonstrated that 9F-CAP specifically targeted cMET protein through molecular docking simulation, surface plasmon resonance (K-d of 40.7 μM), IC50 (168 nM) assays, Annexin V, and cytotoxicity assays. Therefore, the targeted imaging capability of 9F-CAP is of great significance for the preoperative diagnosis of specific cancers.