SPIO标记预设计锚蛋白重复蛋白靶向HER2的磁共振成像研究

Tumor targeted molecular imaging has important theoretical and practical values in cancer diagnosis, treatment options and prognosis evaluation, which make it an essential research field received much attention. Although the number of studies reported in the literature has increased year by year, few reports have translated bench research to clinical practice. The main reasons include not only the sensitivity and specificity of binding molecules, but also the feasibility to prepare, produce, store and transport these targeting probes with high thermostability. Traditionally used antibodies, peptides, and hormonal ligands suffer from some technical limitations that hardly to overcome, which hinder tumor-targeted diagnostic to be widely used in clinic. In the present study, a HER2 binding ankyrin repeat proteins (DARPins) is designed and labeled with SPIO. DARPins are simulant molecules of antibody established by antibody-antigen recognize mechanism. They have high sensitivity and specificity like natural antibodies, and can be produced using prokaryotic expression technology because of the absence of disulfide bonds. The favorable biodistribution and clearance rate make DARPins ideal for labeled-probe preparation. Their high thermal stability facilitates the production, storage and transportation. In short, by preparation and application of the DARPin-based probe, we aim to establish a targeted molecular magnetic resonance imaging method using probes easy to produce, store, transport that can be widely used in clinic, and expect to build a technical bridge to connect molecular recognition theory and clinical practice.

肿瘤靶向分子成像在肿瘤诊断、治疗方案选择和预后评价等方面具有重要的理论和应用价值，也是近年来分子影像学研究的热点课题。虽然文献报告逐年增加，但是很少有进入临床实用阶段的报告。究其原因除了与靶向探针敏感性、特异性相关外，还与靶向分子探针的热稳定性、制剂生产及储运的可行性有关。常规抗体、肽类及激素配体探针都存在一些难以克服技术困难，阻碍了肿瘤分子靶向诊断广泛应用于临床。本课题依据抗体识别抗原的机理研究中建立的分子模拟抗体，拟设计针对HER2的锚蛋白重复蛋白（DARPins）SPIO探针，它具有类似于天然抗体的亲和力和特异性，同时缺少分子内二硫键能够通过原核表达技术生产。DARPins的体内分布和血中清除速度适合于制备标记探针，具有稳定性高、易于制剂生产和储运等优点。试图通过该探针的制备和使用建立一种适合生产、储运和临床广泛应用的磁共振靶向成像方法，在分子识别理论和临床应用之间构建一条技术桥梁。