新型c-Met肺癌靶向分子探针研制及纳米药物治疗评价

Mesenchymal-epithelial transition factor (c-Met) plays an important role in regulation of cell growth and migration in major types of lung cancer and has been identified as a critical therapeutic target. The successful applications of c-Met-targeted molecular imaging will have great advantage on lung cancer diagnosis and treatment. The key challenges of such targeted therapy are technical difficulies on peptide synthesis and radioconjugation of c-Met probe. Based on our previous work, in this study, we will independently radiolabel the polypeptides with 18F-labeled isotope to develop a novel c-Met targeted molecular imaging probe for tumor cells. This study will investigate the biological characteristics，sensitivity of cancer targeting, animal toxicology and safety of the novel probe in vivo and vitro, and will explore the efficacy of treatment by nanoparticles drug combined with c-Met-targeted probe. We will further evaluate the ability of the novel molecular probe to recognize lung cancer and monitor treatment to provide an excellent novel targeted molecular probe for molecular imaging studies. The final goal is to provide a more precise and scientific monitoring method to evaluate lung cancer treatment; timely adjust treatment options, and reasonable treatment.

c-Met分子作为恶性肿瘤诊治关键靶点，几乎对所有亚型肺癌的发生、发展及转归调控发挥重要作用，成功靶向cMet分子成像对肺癌标记诊断、治疗意义重大。但适用于cMet成像的化学分子探针因放射耦连、前体多肽合成等方面技术的限制至今罕有报道。我们结合前期成功研制多肽分子探针对肿瘤原发灶活体定量成像的工作基础；旨在本研究中应用新分段放射化学标记多肽手段，自主研发合成18F同位素标记cMet特异性PET分子成像探针；通过活体内、外定性、定量研究，验证新型探针生物学特性、肿瘤细胞靶向灵敏性、动物毒理学适用性和生物安全性；并通过对多亚型肺癌靶向纳米药物治疗研究，评价新型探针用作肺癌标记诊断及治疗靶点监控的可行性。为肺癌早期诊断提供优质、新型分子探针，为临床更精准、科学监测肺癌治疗及合理施治提供依据。