11C-PD153035 PET/CT筛选非小细胞肺癌EGFR突变和监测EGFR-TKIs疗效的研究

项目名称： 11C-PD153035 PET/CT筛选非小细胞肺癌EGFR突变和监测EGFR-TKIs疗效的研究

项目编号： No.81201827

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 孟雪

作者单位： 山东省医学科学院

项目金额： 23万元

中文摘要： 表皮生长因子受体（EGFR）突变被认为是酪氨酸激酶抑制剂（TKIs）治疗非小细胞肺癌（NSCLC）有效的重要预测指标。目前检测突变的手段多为有创性，不易重复获取,不能全面评价肿瘤组织EGFR状态。分子影像技术是无创性动态检测EGFR的理想方法。我们已成功合成与TKIs相似分子结构的新型PET示踪剂11C-PD153035,证实它能对NSCLC患者的肿瘤病灶显像,具有筛选EGFR状态的潜在可能。在此基础上，本项目拟以DNA测序法和SARMS法检测肿瘤组织EGFR突变作为金标准,验证动物和NSCLC手术患者肿瘤病灶PD153035分子影像参数与肿瘤组织EGFR突变的相关性；验证EGFR-TKIs治疗前、治疗进展或耐药时肿瘤病灶分子影像参数与肿瘤组织、外周血清EGFR突变的相关性并研究治疗前和治疗过程中病灶分子影像参数与疾病变化的关系，从而为EGFR-TKIs患者选择与疗效评价提供新型有效手段。

中文关键词： 非小细胞肺癌；表皮生长因子受体；基因突变；分子影像；靶向治疗

英文摘要： The epidermal growth factor receptor (EGFR) has been extensively investigated as a target of antineoplastic therapy in advanced-stage non-small cell lung cancer (NSCLC). Sequencing of the EGFR gene revealed that most tumors that respond to EGFR kinase inhibitors harbor activating mutations in the EGFR kinase domain. Activating EGFR mutations, including either in-frame deletions in exon 19 or point mutation in exons 20 and 21 play an improtant role in determining responsiveness or resistance to small molecule tyrosine kinase inhibitors (TKIs). Detecting EGFR mutations using tumor tissues obtained via a biopsy or surgical resection is now routinely used to diagnosed NSCLC. In particular, noninvasive tests allow the frequent monitoring of disease progression in patients with the exon 20 mutation. Because a biopsy is an invasive procedure, it is desirable to replace it with a noninvasive procedure. The complexity and limitations of invasive methods of analysis of EGFR mutations prompted the development of novel radiolabeled agents for noninvasive PET imaging, which may help in identificantion of NSCLC paitnets who may benefit from EGFR kinase inhibitors. 11C-labeled 4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline (11C-PD153035), a positron-emitting analog of the EGFR-TKI PD153035, was developed as a noninvasive imagin

英文关键词： non-small cell lung cancer；epidermal growth factor receptor；gene mutation；molecular imaging；target therapy