几乎所有的实体瘤中都有乏氧组织的存在，这使得肿瘤对放疗、化疗无效。以往报道的Tc-99m标记的乏氧显像剂都是将生物还原基团- - 硝基咪唑等和有机配体偶联，再与放射性核素Tc-99m配位，形成一个体积庞大的分子探针，如BMS181321、BRU59-21等。这种体积庞大的放射性核素及有机配体对生物还原基团具有很大的影响，这也是目前乏氧显像剂生物评价效果不佳的主要原因。最近，体内点击化学在国际药物化学、化学生物学领域已经表现出很好的发展态势和其他方法所不具备的优势。在本项目中，我们将体内点击化学应用于放射性乏氧显像剂研究：合成只含有叠氮基的小分子乏氧靶向分子，首先完成乏氧靶向基团在体内的预着靶，然后再注射含有放射性核素的探针进行寻靶，发生体内点击反应，最后完成乏氧组织显像。该方法的应用为发展新型的放射性乏氧显像剂提供了新颖的方法和思路，有可能获得性能优良的乏氧显像剂。

Hypoxic tissue exists in most of the solid tumors， and it decreases the efficacy of radiotherapy and chemotherapy in the treatment of tumor. The Tc-99m-labeled hypoxia imaging agents have been developed to measure the hypoxic tissue, and they consist of the bioreducible group-nitroimidazoles and the organic ligand and the radionuclide technetium-99m, such as BMS181321 and BRU59-21. But, the bioevaluation of these hypoxia imaging agents is unsatisfied since the huge volume of organic ligand and technetium-99m decreases the efficacy of the bioreducible group. Recently, research has focused increasingly on in vivo click chemistry in the field of medicinal chemistry and chemical biology. In this program, the application of in vivo click chemistry in radiolabeled hypoxia imaging agents will be studied: synthesis and pretargeting of small hypoxia-targeting molecule containing the azide group, then administration of radiolabeled probe, finally in vivo click reaction and imaging of hypoxia. In a word, in vivo click chemistry provides the new method and idea to develop the novel radiolabeled hypoxia imaging agents, and it is possible to gain the successful and satisfied hypoxia imaging agent.