基于叶酸及叶酸拮抗剂的高性能小分子磁共振造影剂的设计合成及其肿瘤诊疗应用研究

逐年上升的肿瘤发病率向磁共振成像技术提出了严峻挑战。为了提高磁共振成像的灵敏度和靶向性以应对临床精确诊断的需求，本项目拟将叶酸靶向基团与小分子造影剂结合起来，设计合成高性能的叶酸靶向造影剂探针，用于对叶酸受体高表达的肿瘤进行高灵敏靶向磁共振成像。在此基础上，发展多种基于叶酸拮抗剂的兼具诊疗功能的小分子造影剂探针，以期对叶酸受体高表达的肿瘤同时实现成像监测、预后分析和有效治疗。本项目所发展的高性能小分子造影剂有望为肿瘤的早期精确诊断、实时监测与积极治疗提供有效方案。

The increasing annual incidences of tumors pose a serious challenge for magnetic resonance imaging (MRI). To improve both targetability and sensitivity of MRI to meet the needs of accurate clinical diagnosis, this project is aimed to design and synthesize high-performance folate-based contrast agents for high-sensitivity targeting MRI of tumors that overexpress folate receptors (FR) by conjugating folic acid with small molecular contrast agents. On the basis of these contrast agents, a new type of contrast agents with both diagnostic and therapeutic functions, folate-antagonist-based contrast agents, will be developed for simultaneous monitoring, prognosis, and treatment of tumors that overexpress FR. The high-performance targeting contrast agents developed by this project will provide solutions for early and accurate diagnosis, real-time monitoring, and active treatment of tumors.