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Introduction Epidermal growth factor receptor(EGFR)is very important receptor in normal cell,however the mutation of it leads to drug resistance in many carcinomas especially in non-small cell lung cancer(NSCLC)which makes it a significantly important factor in the treatment of NSCLC.It is urgent to develop a novel noninvasive method to identify the patients who is the most suitable for EGFR-targeted therapy and monitor the EGFR mutation.Tyrosine kinase inhibitors(TKIs)have experienced a tremendous boost in the last decade.For non-small cell lung cancer(NSCLC),the effectiveness of TKIs is dependent on the mutational status of epidermal growth factor receptor(EGFR).The exon 19 deletion as well as the L858R point mutation leads to an excellent sensitivity to TKIs such as erlotinib and gefitinib; however,despite initial good response,most patients are unsuited for the treatment of TKIs.Hence,a novel EGFR tyrosine kinase inhibitor(IRS,an analogue of gefitinib)was developed labeled with fluorine-18 to evaluate its potential as a TKI PET tracer to identify drug-sensitive patients.Methods 18F-IRS was synthesized via a one-step radiofluorination in this study.Cell uptake was performed with four cell lines : HCC827(a treatment-sensitive exon 19 deleted mutant),H358(an EGFR-WT cell line),H1975(an acquired treatment-resistant L858R/T790Mmutation),and H520(an EGFR low expression cell line).The biological characterization of18F-IRS was performed with both normal mice and tumor xenografts(HCC827,H1975,H358 and H520).Results 18F-IRS can be prepared efficiently with a yield of 15–20%.The one-step radiolabelling followed by preparative HPLCpurification provided with radiochemical purity >98%(n>3)in a total synthesis time of about 2 hours.The lipid solubility of 18FIRS is reflected by a partition coefficient(log P)of-0.673475±0.0962.The uptake of18F-IRS by HCC827 cells was significantly higher than those by H358,H1975,and H520cells,and reduced obviously at the presence of 100μM of gefitinib in culture medium.According to bio-distribution of normal mice,18F-IRS was mainly metabolized through the urinary system.The accumulation of 18F-IRS in HCC827 tumor was reached 2.668±0.4%ID/g,about 2 fold of H1975(1.371±0.223%ID/g)and H358(1.108±0.18%ID/g)after injected 18F-IRS 1h.Conclusions 18F-IRS has the potential for imaging mutated EFFR especially 19 exon deleted mutation in NSCLC in vivo.18F-IRS can specificity bind with mutated EGFR,therefore it may be expected to achieve the molecular classification of NSCLC in vivo and guide the targeted therapy in clinical.