α核素At-211是最适宜于肿瘤靶向内放射治疗的理想核素之一。选择优良的载体和建立适宜的标记方法是At-211靶向药物研究的基础与关键。本课题拟以SPC或TCP为双功能偶联剂，通过先将其与蛋白质或多肽结合，再进行At-211标记的研究思路，以降低辐解效应，提高标记率，建立一条适合于At-211标记小分子多肽的一步间接方法。在此基础上，进行融合肽VHCDR1-VHFR2-VLCDR3的At-211标记及体内外动物实验研究，以期将我校近期自主合成并对恶性淋巴瘤具有良好亲和性的这种融合肽的靶向作用和At-211的极强细胞毒性相结合，实现At-211标记VHCDR1-VHFR2-VLCDR3用于恶性淋巴瘤的靶向治疗研究。研究结果不仅可为At-211标记蛋白质或多肽的方法提供一条新的思路，为At-211标记小分子肽类靶向治疗药物的深入研究奠定良好基础，而且对推动肿瘤的核素靶向治疗具有显著的现实意义。

As a cyclotron-produced nuclide and α-emitter, astatine-211 is particularly attractive for application to targeted radionuclide therapy (TRT) of cancer, especially for treatment of micrometastatic disease, cancer that is resistant to other forms of radiation, and cancer contained in compartmental spaces, due to the unique cytotoxic properties of the α-particles. Therefore, growing efforts have been devoted to the targeted radiotherapy experiments of At-211 labelled radiopharmaceuticals since 1970s, and great progress has been got more recently. However, there still exist some obstacles to further investigation of tumor targeted radiotherapy with At-211. Of which, the lack of more wonderful tumour-targeting carriers and more suitable labeling methods stills are the most important and key issues. The first goal of this proposal is to attempt a one-step procedure for At-211 labeling of proteins and peptides with high labeling yileds and low rdiolytic effects, especially for peptides with small molecular, by using N-succinimidyl 5-(tributylstannyl) -3-pyridinecarboxylate (SPC) or 2, 3, 5, 6-tetrafluorophenyl 3-(nido-carboranyl) propionate (TCP) as bi-functional linkers, and conjugating proteins or peptides with the linkers first, then labling with At-211. Aften then, a novel fusion peptide with high affinity to malignant lymphoma, which first synthesized in Sichuan University, is proposed to be labelled with At-211, and the At-211 labelled fusion peptide will be evaluated in vitro and vivo, included vitro and vivo stability, the biodistribution behavior and the targeted radiotherapy effects in animal model. By this project, a new method for At-211 labeling of proteins or peptides would be established and targeted radiotherapy of the At-211 labelled new fusion peptide for malignant lymphoma would be first investigated in animal model. All the result would be very useful to further study of tumor targeted radiotherapy with At-211 and other nuclides labelled compunds, especially with At-211 labelled small molecular peptides.