Synthesis and preliminary evaluation of F-icotinib for EGFR-targeted PET imaging of lung cancer.

Epidermal growth factor receptor (EGFR) has emerged as an attracting target in the field of imaging and treatment for non-small cell lung cancer (NSCLC). Radiolabeled EGFR-tyrosine kinase inhibitors (EGFR-TKIs) specifically targeting EGFR are deemed as promising probes for the imaging of NSCLC. This study aimed to label icotinib (one kind of EGFR-TKI) with F through click reaction to develop a new EGFR-targeting PET probe-F-icotinib. F-icotinib was obtained in 44.81% decay-corrected yield in 100 min synthesis time with 34 GBq/μmol specific activity and >99% radiochemical purity at the end of synthesis. The identity of the product was confirmed by co-injection with F-icotinib and F-icotinib. The Log P was 1.28 ± 0.04 (n = 6). The tracer displayed excellent stability after incubation for 4 h in vitro. F-icotinib showed satisfying binding ability to A549 NSCLC cells, which could be inhibited by icotinib. PET imaging studies demonstrated a specific uptake of the radiotracer (0.90 ± 0.24% ID/g) in A549 tumor-bearing mice, while lower uptake was observed in heart, lung and spleen at 1.5 h post injection. Inmunohistochemical staining confirmed that the A549 tumor was EGFR-positive. Therefore, we considered that F-icotinib was a highly promising compound for EGFR-based tumor PET imaging.