氟-18标记的整合素avb6-半胱氨酸结PET分子探针的研制

项目名称： 氟-18标记的整合素avb6-半胱氨酸结PET分子探针的研制

项目编号： No.81201141

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 刘弘光

作者单位： 东北大学

项目金额： 23万元

中文摘要： 整合素avb6是分子影像学领域的新兴肿瘤靶点，它在多种癌症中高表达，但在正常组织中表达水平很低。目前针对整合素avb6的分子探针较少，显像效果也并不理想。本项目在靶向整合素avb6的"胱氨酸结"分子探针的基础上，根据"胱氨酸结"的体内药代动力学特点，优化放射性核素的选择，并采用具有临床转化潜力的氟化铝一步法放射性标记，有望研发出具有临床转化潜力的整合素avb6胱氨酸结分子探针。 申请人在分子探针的研发方面具有丰富的经验。从分子探针的合成、修饰、放射化学标记，到体外细胞学检测、体内PET显像和体内分布研究，申请人与全体参与人员对项目的顺利完成有着充分的准备和信心。武汉大学组合生物合成与新药发现教育部重点实验室的一流实验条件为本项目的顺利实施提供了有力保障。

中文关键词： 分子影像；分子探针；肿瘤；亲合体；纳米探针

英文摘要： Integrin avb6 is a cell surface receptor that widely overexpressed on many cancer cells like breast, lung, colon, skin, ovarian, and pancreatic cancers, but it only express at low levels in healthy tissue. Recently integrin avb6 have been evaluated as a novel clinical biomarker. Systine knot are highly stable peptides with more than 3 pairs of systine forming a "knot" structure. Its tight structures give it favorable properties to be used as a molecular scaffold for new PET imaging probes. Some systine knot peptides have been engineered for specifically binding to integrin avb6 as molecular imaging probes and demonstrated their effectiveness in 64Cu-DOTA microPET studies. Here we propose to evaluate 18F-labeled cystine knot peptides, R01, R02 and S02, for microPET imaging of integrin avb6 overexpressed cancer xenografts in mice.Cystine knot peptides will firstly be synthesized by solid phase Fmoc chemistry. A conjugation with NOTA will be carried out followed by purification. Cystine knot peptides will be labeled using one-step AlF-NOTA method then be purified by radioHPLC. Serum stability and cell uptake assays will be studied for these 18F labeled probes. Nu/Nu Nude mice bearing tumors with different levels of integrin avb6 expressions will be used as animal models. BxPC-3 pancreatic cancer cells and A431 epi

英文关键词： molecular imaging；molecular probe；tumor；affibody；nano probe