新型锝-99m标记的硝基咪唑类SPECT肿瘤乏氧分子探针的研究

Tumor hypoxia prevails on the solid tumor and decreases the therapeutic effect of radiotherapy and chemotherapy. Tumor oxygenation can be assessed by polarographic oxygen electrodes directly, but it can not be used for clinical measurement because of its invasive nature, inconvenience, limitation for accessiable tumor and operator dependence. Noninvasive method like nuclear medicine imaging assesses tumor hypoxia at molecule level, provides three dimensional images of tumor hypoxia area, however, it is difficult to carry out right now in our country due to lack of ideal imaging radiopharmaceuticals or restricted supply of radionuclide. .The project aims to design a series of novel tumor hypoxia imaging probes containing different nitroimidazole groups (2-/4-nitroimidazole). The characteristic of the structure is leading-in alkyl chain or PEGs on the basis of nitroimidazole group, then reacted with 1,5,9-triazacyclododecane-1,5-dicarboxylate to form eight precursors and they were labled with 99mTc(CO)3 core to obtain the corresponding eight complexes.The potential of these complexes as novel SPECT tumor imaging agents will be evaluated by testing their physicochemical properties and biological properties. The validity and practicability can be demostrated by SPECT imaging in tumor-bearing animals. The project developed tumor hypoxia imaging agents with independent intellectual property rights which promise to provide a new and effective technique for early diagnosis of tumor hypoxia combined with clinical evidence of dysfunction and preliminary lay the clinical foundation for achieving the goal of transforming in the future.

肿瘤乏氧（tumor hypoxia）在固体瘤中普遍存在，它会降低放疗、化疗的治疗效果。氧电极法可以直接探测肿瘤乏氧程度，但其具有侵入性、局限性，存在采样误差。核医学显像具有无创特性，能在分子水平上探测肿瘤乏氧程度，提供肿瘤乏氧的三维图像，但由于缺乏理想的显像药物或受到标记核素供应限制，目前在国内临床上难以开展。.本项目旨在构建系列含不同硝基咪唑基团（2-/4-硝基咪唑）的新型肿瘤乏氧显像探针，在硝基咪唑侧链引入烷基链或聚乙二醇链，与大环多胺TACD二酸相连，形成8种不同标记前体，并进行99mTc(CO)3核标记。通过放射化学性质测定、体外细胞实验和动物体内分布实验筛选性能最优的肿瘤乏氧显像药物，并进行肿瘤模型的SPECT显像研究，以验证其生物性能。本项目研制的肿瘤乏氧放射性药物具有自主知识产权，有望早期发现肿瘤乏氧特性，为临床提供组织功能障碍的依据，并为将来实现临床转化目标初步奠定基础。

肿瘤乏氧（tumor hypoxia）在固体瘤中普遍存在，它会降低放疗、化疗的治疗效果。氧电极法可以直接探测肿瘤乏氧程度，但其具有侵入性、局限性，存在采样误差。核医学显像具有无创特性，能在分子水平上探测肿瘤乏氧程度，提供肿瘤乏氧的三维图像，但由于缺乏理想的显像药物或受到标记核素供应限制，目前在国内临床上难以开展。.本项目旨在构建系列含不同硝基咪唑基团（2-/4-硝基咪唑）的新型肿瘤乏氧显像探针，在硝基咪唑侧链引入烷基链或聚乙二醇链，与大环多胺TACD二酸相连，形成8种不同标记前体，并进行99mTc(CO)3核标记。通过放射化学性质测定、体外细胞实验和动物体内分布实验筛选性能最优的肿瘤乏氧显像药物，并进行肿瘤模型的SPECT显像研究，以验证其生物性能。本项目研制的肿瘤乏氧放射性药物具有自主知识产权，有望早期发现肿瘤乏氧特性，为临床提供组织功能障碍的依据，并为将来实现临床转化目标初步奠定基础。