基于可活化胶原蛋白结合肽的肿瘤MMP-14酶活性核素显像研究

项目名称： 基于可活化胶原蛋白结合肽的肿瘤MMP-14酶活性核素显像研究

项目编号： No.81201119

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： 郑磊

作者单位： 中国人民解放军第三军医大学

项目金额： 23万元

中文摘要： 基质金属蛋白酶（matrix metalloproteinases, MMP）能够促进肿瘤的侵袭、转移与血管生成，其中MMP-14具有关键作用，并已成为抗肿瘤治疗的重要靶标。探测MMP-14在肿瘤中的酶活性，对指导临床实施MMP-14抑制剂抗肿瘤治疗与疗效评价具有重要意义，而可活化分子探针的核素显像是实现在体显示MMP-14酶活性的解决途径。本课题拟将99mTc标记的胶原蛋白结合肽（HVWMQAP）和能够抑制其与胶原蛋白结合的胶原蛋白样多肽(GPHyp)5，分别构建于能被MMP-14特异性酶切的多肽序列两端。当(GPHyp)5在肿瘤细胞表面MMP-14酶切作用下脱落后，HVWMQAP暴露活化，并与肿瘤间质中的胶原蛋白结合后滞留，从而实现MMP-14酶活性的在体分子影像。本课题通过研究该探针的体、内外生物活性与动物显像，为实现MMP-14酶活性的分子影像诊断提供理论依据。

中文关键词： 基质金属蛋白酶-14；胶原蛋白结合肽；I型胶原蛋白；放射性核素显像；纤维化

英文摘要： Matrix metalloproteinases (MMPs) can promote tumor invasion, metastasis and angiogenesis. Membrane-expressed MMP-14 is in the leading role ammong them,and it has become an important target for antineoplastic therapy. Detection of MMP-14 enzyme activity in tumor in vivo is very important for guiding the therapy of MMP-14 inhibitors and evaluating its curative effect, and radionuclide imaging of activable molecular probe is the way to display MMP-14 enzymatic activity in vivo. This study will join the 99mTc-labeled collagen-binding peptide(HVWMQAP) and collagen-like peptide (GPHyp)5 which can inhibit combination between HVWMQAP to the both ends of a peptide specifically sheared by MMP-14. After the (GPHyp)5 sheared by the MMP-14 on the tumorcell surface, HVWMQAP is exposed and activated, and combine with collagens in the tumor interstitial. Accordingly, molecular imaging of the enzymatic activity of MMP-14 is achieved in vivo. This study will research physical, chemical and biological properties of the molecular probe in vitro and in vivo, and imaging in animals, to provide the theory basis of molecular imaging diagnosis on MMP-14 enzyme activity.

英文关键词： Matrix metalloproteinase -14；Collagen-binding peptide；Collagen type I；Radionuclide imaging；Fibrosis