乏氧是实体瘤的重要特征之一。乏氧显像对肿瘤的诊断治疗非常重要。常规乏氧显像剂一般为放射性标记的硝基咪唑类衍生物，但是该类显像剂效果并不理想。最近研究表明，放射性核素标记的碳酸酐酶抑制剂-磺酰胺类药物也可用于乏氧显像。我们初步考察了磺酰胺类药物对硝基咪唑类乏氧显像剂的细胞摄取影响，发现乏氧细胞摄取明显提高。磺酰胺与硝基咪唑化合物在乏氧细胞摄取中有可能存在协同效应，将这两种基团偶联也可能形成效果更好的双靶点乏氧显像剂。本项目希望通过在放射性氟、碘标记的硝基咪唑类乏氧显像剂上偶联磺酰胺基团，结合生物评价结果，筛选出新的双靶点乏氧显像剂，并研究乏氧细胞摄取的机理，为设计、研制新型的乏氧显像剂提供依据。

Hypoxia is an important feature of solid tumor. Hypoxia imaging plays an important role in diagnosis and therapy of tumors. Traditional hypoxia imaging agents are radiolabed nitromidazoles, but these imaging agents are not very ideal. Recent studies have shown that radiolabeled sulfonamides, carbonic anhydrase inhibitors, can also be used in hypoxic imaging. We have investigated the effect of sulfonamides on the cellular uptake of nitroimidazole-based hypoxic imaging agents, and it was found that the uptake in hypoxic cells was significantly increased. There may be a synergistic effect between sulfonamide and nitroimidazole compounds in the of hypoxic cellular uptake, these two groups may be coupled to form the dual-targeted hypoxia imaging agents with better effects. In this project, new dual-targeted hypoxia imaging agents containing sulfonamide and nitroimidazole groups will be synthesized, and radiolabeled with fluorine-18 or iodine-124/125/131. Based on the in vivo and in vitro results, the most excellent dual-targeted hypoxia imaging agent will be found. Meanwhile, the mechanism of their accumulation in hypoxia will be explored. The results are very useful for design the novel hypoxia-imaging agents.