我国非小细胞肺癌发病率持续上升，对不能手术的中晚期患者来说治疗手段少、预后差，因此研发新的治疗方法是当今热点。整合素亚型αvβ6在非小细胞肺癌中高表达，且表达高低与肿瘤侵袭和预后密切相关，是极具潜力的重要靶点。然而目前大部分靶向整合素αvβ6的探针实验结果不理想。前期工作中，我们用放射性核素68Ga标记与整合素αvβ6具有高亲和性和特异性的“半胱氨酸结”突变体，并进行小动物PET肺癌显像，结果显示图像质量好，肿瘤摄取高，血浆清除快，肿瘤与本底比值高。这为研发非小细胞肺癌靶向诊疗提供了新策略。因此，本课题拟用放射性核素177Lu标记“半胱氨酸结”肽突变体（S02和R01），通过建立非小细胞肺癌动物模型（包括人源肿瘤异种移植动物模型），进行放射性药物小动物SPECT/CT显像、放射性靶向治疗及疗效评估，实现诊疗一体化，为中晚期肺癌患者提供新的治疗方法。

The incidence of non-small cell lung cancer (NSCLC) in China continues to increase. However, for the patients with inoperable advanced NSCLC, therapeutic options are quite limited with poor prognosis. Thus, it is very important to develop new therapeutic methods for NSCLC. Integrin subtype αvβ6 is highly expressed in NSCLC, and its expression level is closely related with the tumor invasion and prognosis, which is a potentially important target. However, at present, the experimental results of most probes targeting integrin αvβ6 were not satisfactory. In our previous study, cystine knot peptide mutant targeting to integrin αvβ6 with high affinity and specificity was radiolabeled with 68Ga, and subsequent small animal PET imaging was performed in animal models with NSCLC. The result demonstrated that the image quality was good, the radiotracer uptake of tumor was high, the probe was quickly cleared by the plasma, and the ratio of tumor to background was high. It provides a new strategy for us to develop the diagnosis and therapy for NSCLC. Therefore, in this study, we plan to radiolabel cystine knot peptide mutants S02 and R01 with 177Lu, and establish animal models with NSCLC, including patient-derived xenografts. The animal models with NSCLC will be imaged by small animal SPECT/CT postinjection of 177Lu radiolabeled cystine knot peptide mutants, and the radioactive targeted therapy will be performed and evaluated to achieve the integration of diagnosis and treatment. It may provide new therapeutic methods for the patients with advanced NSCLC.