晚期非小细胞肺癌（NSCLC）患者中适于靶向治疗的不足20%，其中有效的占60-80%，总体获益比例仅为12-16%。此外，几乎所有患者都会随治疗的深入出现继发性耐药。以放射性核素标记多肽探针为载体的放射靶向治疗为晚期NSCLC的治疗提供了新的思路。但目前大部分肽类药物在体内的清除速率快、半衰期短，因此在肿瘤组织中摄取不高、滞留时间短，影响了其作为放射性治疗药物的临床转化。本研究针对以NSCLC高表达的整合素αvβ3为靶标，设计以结合伊文思蓝（EB）的RGD多肽（EB-RGD）为放射性靶向探针，通过EB与体内白蛋白的结合延长靶向探针在体内的循环时间，提高以RGD为载体的放射靶向治疗效果。本项目拟采用治疗核素177Lu标记EB-RGD构建内照射靶向治疗探针，进行NSCLC模型的放射靶向治疗；采用显像核素64Cu标记同一靶向分子构建诊断性显像筛选探针，实现“筛选-治疗”一体化放射性探针的构建。

Only 12-16% patients with advanced non-small cell lung cancer (NSCLC) can benefit from targeted therapy. Furthermore, secondary drug resistance has occurred in almost all patients with time and treatment. At this moment of challenge, tumor targeted radiotherapy with the radiolabeled peptide probe provides a new idea for the treatment of advanced NSCLC. However, most of peptide probes are characterized by the fast renal excretion and short half-life in blood, such unfavorable pharmaceutical properties leads to low tumor uptake and prevent their translation into clinical settings for being used as a radiotherapeutic agent. In this study, we are going to propose a novel platform for developing a long-lasting radiotherapeutic agent by conjugating a small molecular albumin binding moiety, truncated Evans blue (EB), to RGD peptide. Here, we will describe the novel EB derivative that, on conjugation with targeting agents, results in an enhanced half-life in blood. Through radiolabeling with 64Cu or 177Lu, we are going to evaluate whether the EB-conjugated RGD peptide (EB-RGD) could be of use as an imaging probe for the pre-treatment screening and a radiotherapeutic agent for the targeted radiotherapy of integrin αvβ3-expressing NSCLC. Through this investigation, we wish to establish the “prescreening-therapy” radiolabeled peptide probe for advanced NSCLC and propose a novel strategy for enhancing tumor uptake of αvβ3-targeted probe.