New Chelators for Less-Developed and 'Heavy' Radioactive Metal Isotopes

该项目将以螯合物设计和合成一系列放射性核素为特色，这些核素以前很少开发配体化学，并且位于周期表的低端，例如223 Ra，212 Pb，225 Ac，213 Bi和227 Th。这些放射性同位素提供了一系列成像、诊断和治疗性质，这些性质目前由于缺乏合适的螯合剂以及缺乏放射性同位素本身的可用性而未得到充分利用。这些金属中的许多已经以其简单的卤化物、硝酸盐或氢氧化物化合物状态使用，但是文献中已知的稳定的螯合络合物真实的缺乏。在这个项目中，学生将准备一系列大环“冠”配体，其特征是在环系统内或作为侧基的一系列供体杂原子，这可以使放射性金属的“硬-软”性质的定制。将选择最有前途的螯合剂用于与肽或抗体的生物缀合，并进行一系列放射性标记，体外和体内实验，以评估这些新的靶向放射性示踪剂的生物学功效。合成化学将在帝国理工学院进行，而放射性标记生物实验将在国王学院进行，并通过国家核实验室的合作者进行。

This project will feature the chelate design and synthesis of a range of radionuclides for which previously very little ligand chemistry has been developed, and are situated towards the lower end of the periodic table e.g. 223Ra, 212Pb, 225Ac, 213Bi and 227Th. These radio isotopes offer a range of imaging, diagnostic and therapeutic properties which have currently been underutilised by the lack of suitable chelators, and the lack of availability of the radioisotopes themselves. Many of these metals have been utilised in their simple halide, nitrate or hydroxide compound state, but there is a real dearth of stable chelate complexes known in the literature. In this project, the student will prepare a range of macrocyclic 'crown' ligands featuring a range of donor heteroatoms either within the ring system or as pendant groups, which can enable a tailoring of the 'hard-soft' nature of the radiometals. The most promising chelators will be chosen to take forward for bioconjugation to a peptide or antibody, and subjected to a range of radiolabelling, in vitro and in vivo experiments to evaluate the biological efficacy of these new, targeted radiotracers. The synthetic chemistry will be carried out at Imperial College, whilst radiolabelling biological experiments will be undertaken at King's College and via collaborators at the National Nuclear Laboratory.