关键词: ^99mTc-HYNIC-MPG, 突变EGFR, 酪氨酸激酶抑制剂, 非小细胞肺癌, SPECT, 分子影像

Abstract: Objective The objectives of this study were to synthesis a specific probe ^99mTc-HYNIC-MPG targeting mutant epidermal growth factor receptor(EGFR)and use it to determine the EGFR mutation status of non-small lung cell cancer(NSCLS)in real-time and in vivo.Methods One-step synthesis of ^99mTc-HYNIC-MPG was divided into human non-small cell lung cancer PC9(experimental group,exon 19 deletion),H358(control group,EGFR wild type),H520(control group,EGFR negative),and H1975(T790m/L858R secondary mutation).The four cell lines were subjected to ^99mTc-HYNIC-MPG probe for cell uptake,release and blocking experiments.Four different cell lines were used to construct animal models of tumor-bearing nude mice,and single-photon emission computed tomography(SPECT)imaging and biological distribution were performed at 1,2,4,and 6h.PD153035(100mg/kg)was used to verify whether it could block the uptake of the probe by PC9 cells for a tumor-bearing mouse model.Results The labeling rate of ^99mTc-HYNIC-MPG probe was as high as 98%.PC9 cells had the highest uptake rate of ^99mTc-HYNIC-MPG,which could reach(23.79±0.63)%.PD153035(100μmol/L)could block uptake and the uptake rate was reduced to(1.90±0.06)%.The distribution experiment in vivo showed that PC9 cells reached a peak(7.20±0.27)%ID/g at 2h,while the tumor uptake of H358,H520 and H1975 cell lines was significantly lower.The SPECT imaging results also showed that the tumor of the PC9 cells tumor-bearing mouse model had a high uptake of ^99mTc-HYNIC-MPG.Conclusion The ^99mTc-HYNIC-MPG probe is specific and targeted,can specificity bind to the EGFR mutation with deletion of exon 19,and is expected to truly achieve in vivo molecular typing of lung cancer.

Key words: ^99mTc-HYNIC-MPG, Mutated EGFR, Tyrosine kinase inhibitor, Non-small cell lung cancer, SPECT, Molecular imaging