靶向细菌性感染的放射性核素标记抗菌肽衍生物的制备和显像研究

抗菌肽具有靶向细菌细胞壁的特性，因此围绕抗菌肽来构建新型靶向细菌的放射性核素标记分子探针具有可行性和重要意义。为研制特异性好且便于推广的细菌性感染显像剂，本项目选择抗菌肽UBI 29-41为研究对象，一方面选择99mTc为SPECT核素，设计合成系列含异腈的UBI 29-41衍生物，经 [99mTc(I)]+和[99mTc(CO)3(H2O)3]+标记制备相应的99mTc标记物；另一方面选择18F为PET核素，合成含NOTA及其衍生物的UBI 29-41偶联物，经Al18F标记制备相应的18F标记物。通过配体结构修饰和药盒化标记策略的优化以期得到稳定性高、靶向性佳、便利性好的用于细菌性感染显像的新型分子探针，将其与SPECT/PET分子影像技术结合可实现对细菌性感染的精确可视化诊断以及抗菌药物疗效的监测。项目注重需求与创新密切结合，将为转化医学和精准医疗的实现奠定良好的基础。

Antibacterial peptides have the properties of targeting bacterial cell walls, so the construction of novel radiolabeled antibacterial peptides as targeting bacterial infection molecular probes is feasible and has important significance. In order to develop bacterial infection imaging agents with good specificity and convenient clinical application, in this project, by choosing antimicrobial peptide UBI 29-41 as the research object, on the one hand, 99mTc will be selected as a SPECT nuclide and a series of UBI 29-41 antibacterial peptide derivatives containing isonitrile group will be synthesized. The corresponding 99mTc labeled complexes can be prepared by radiolabeling the UBI 29-41 derivatives with [99mTc]+ and [99mTc(CO)3(H2O)3]+ cores. On the other hand, by choosing 18F as a PET nuclide and the synthesis of several UBI 29-41 antibacterial peptide conjugates containing NOTA (1,4,7-triazacyclonane-1,4,7-triacetic acid) and its derivative, the corresponding 18F labeled complexes can be achieved by radiolabeling the above conjugates with Al18F. The novel molecular probes for bacterial infection imaging with high stability, good targeting ability and great convenience will be expected to obtain through ligand structure modification and optimization of using kit formulation labeling strategy. Combining them with SPECT/PET molecular imaging technology will enable accurate visualization of bacterial infections and monitoring of antibacterial efficacy. This project emphasizes the close combination of originality and demand, which will lay a good foundation for the realization of translational medicine and precision medicine.