酪氨酸激酶抑制剂（TKIs）在细胞内与ATP 竞争结合EGFR 酪氨酸激酶活性区，从而抑制EGFR 的自身磷酸化及其下游信号通路的传导，达到抑制肿瘤增殖、侵袭及转移的目的。对EGFR-TKI治疗有效的患者中，EGFR基因突变率可达77%，突变丰度可以预测TKIs治疗晚期非小细胞肺癌的疗效。目前能同时识别19外显子缺失、L858R突变和 L858R/T790M突变的分子探针的合成和应用，国内外尚无报道。本项目拟合成正电子放射性EGFR分子探针11C-AZD9291和18F-PEG-AZD9291，用于区分以上三种突变的EGFR与野生型EGFR，并完成质量控制实验、细胞摄取实验、药代动力学实验以及 PET/CT 扫描等一系列临床前实验工作。实现活体状态下对突变EGFR表达水平与状态的实时、直观成像，为其应用于EGFR分子分型的诊断、指导临床治疗方案奠定实验基础。

Tyrosine kinase inhibitors (TKIs) and ATP competitive combine with epidermal growth factor receptor (EGFR) intracellular tyrosine kinase domain of the ATP combined sites, thus inhibiting EGFR phosphorylation and the downstream signaling pathways, reach the purpose of inhibiting tumor proliferation, invasion and metastasis. Gene sequencing studies revealed that EGFR gene mutation rate can reach 77% for the patients of EGFR - TKI effective treatment, curative effect for the treatment of advanced non-small cell lung cancer (NSCLC) by TKIs can be predicted according to mutation abundance. The selectivity of positron radioactive EGFR molecule probes were low between wild type and mutant, also could not identify L858R/T790M dual mutation EGFR so far. There was no synthesis and application of molecular probes which can identify all that eliminate amino acids 747-750 (caused by small deletions in exon 19), L858R mutation and L858R/T790M mutation EGFR were reported at home and abroad. This project intends to develop positron radioactive EGFR molecule probes 11C-AZD9291 and 18F-PEG-AZD9291, which will be used to distinguish mutation EGFR from wild type. Quality control, cell uptake, pharmacokinetic experiment, PET/CT scan and a series of preclinical experiment will be performed as well. Thus the assessment of these two pet tracers we offered will lay the foundation of diagnosis in real-time and intuitive imaging of EGFR expression, which will guide clinical treatment for future.