最新研究发现廉价的传统戒酒药双硫仑具有良好的抗肿瘤效能，双硫仑在体内代谢为二硫代氨基甲酸酯后能与金属铜（Cu）相螯合形成双二硫代氨基甲酸铜复合物（bis (diethyldithiocar bamate)-copper，CuET），该复合物能特异性靶向p97–NPL4–UFD1通路，产生明显的抗肿瘤效能。我们在成功建立了正电子核素64Cu螯合标记法的基础上，拟用64Cu取代Cu参与CuET合成，研制一种靶向p97-NPL4-UFD1通路的PET分子探针64Cu-CuET，用microPET/CT显像验证其对高表达p97-NPL4-UFD1的恶性肿瘤的显像能力，创建一种将肿瘤p97-NPL4-UFD1通路可视化的新型PET/CT分子影像技术，用以指导双硫仑抗肿瘤治疗。在此基础上，用肿瘤靶向多肽DA7R和PEG修饰第5代聚酰胺胺树状大分子金纳米颗粒载体，用于负载64Cu/Cu-CuET复合物，建立一种既能将大量CuEF输送到肿瘤靶位以提高治疗效果又能用PET进行可视化研究的诊疗一体化新模式。此研究具有重要的科学意义，将可促进基于p97-NPL4-UFD1通路的显像和治疗进展。

Disulfiram (DSF)， an old alcohol-aversion drug, was currently reported to be repurposed for treating the malignant tumors. The active metabolite of this drug, named diethyldithiocarbamate (DTC) , can form a DTC–copper complex (bis (diethyldithiocarbamate)–copper (CuET)) with copper, which will target to p97–NPL4–UFD1 pathway in malignant tumors with an order of magnitude higher comparing to normal tissue and induces an apoptosis-independent cell death. However, there are two problem needed to be resolved before it will be introduced to clinic. Firstly, it needs to determine which patients can obtain the best benefit from this treatment. Secondly, it needs more measures to improve the treatment effect of DSF. Based on the successful establishment of a chelating radiolabeling methodology for positron emitters of 64Cu, in this project, we will innovatively develop a novel PET probe （64Cu-CuET）using 64Cu as a substitute of Cu to participate in CuET synthesis. After that, we will evaluate whether this novel probe can noninvasively visualize the expression of p97–NPL4–UFD1 in tumors by microPET/CT. Furthermore, we will design a high hydrophilic and tumor targeting vector by modifying the dendrimer gold nanoparticle with tumor targeting peptide DA7R and hydrophilic linker PEG, which can encapsulate 64Cu/Cu-CuET complex. This carries cargo of 64Cu/Cu-CuET can be served as theranostics tool, not only for delivering more CuEF to the tumor to enhance the therapeutic effect, but also for visualizing the targeting capacity of the vector in vivo by microPET/CT. This research work will help to guide the antitumor treatment of disulfide and may establish a more effective treatment strategy.