Development and Evaluation of (18)F-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC.

To prepare and evaluate a new radiotracer (18)F-IRS for molecular imaging mutant EGF Receptors in vitro and vivo. Uptake and efflux of (18)F-IRS were performed with four NSCLC cell lines including HCC827, H1975, H358 and H520. In vivo tumor targeting and pharmacokinetics of the radiotracers were also evaluated in HCC827, H1975, H358 and H520 tumor-bearing nude mice by PET/CT imaging. Ex vivo biodistribution assays were performed to quantify the accumulation of (18)F-IRS in vivo. We also performed (18)F-IRS PET/CT imaging of three patients with NSCLC. We labeled this small molecule with QD620 for flow cytometry and confocal imaging analyses. The uptakes of (18)F-IRS by HCC827 and HCC827 tumors were significantly higher than those of H358, H1975 and H520, and they were reduced by the addition of 100 μM of gefitinib. Biodistribution experiments showed an accumulation of (18)F-IRS in tumors of HCC827 xenografts. Flow cytometry and confocal imaging with QD620-IRS further demonstrated that binding specifically to HCC827 cells. (18)F-IRS accumulation was preferential in the tumor, which was NSCLC with responsive EGFR exon 19 deleted. (18)F-IRS showed high binding stability and specificity to 19 exon deleted EGFR mutation in vitro and vivo.