Open AccessDevelopment and Evaluation of 18F-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC
Author(s) -
Yan Song,
Zunyu Xiao,
Kai Wang,
Xiance Wang,
Chongqing Zhang,
Fang Fang,
Xilin Sun,
Baogen Shen
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-01443-7
Subject(s) - in vivo , biodistribution , flow cytometry , gefitinib , chemistry , ex vivo , molecular imaging , cancer research , in vitro , epidermal growth factor receptor , microbiology and biotechnology , receptor , biology , biochemistry
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 .