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Flexible Peptide Decorated Polyaminocarboxylate Ligands for Selective Extraction of Radiotherapeutic Metals for Targeted Alpha Cancer Therapy

用于选择性提取放射治疗金属以用于靶向α癌症治疗的柔性肽修饰的聚氨基羧酸盐配体

基本信息

批准号：
2786514
负责人：
金额：
--
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2786514
关键词：
Flexible Peptide Decorated Polyaminocarboxylate Ligands

项目摘要

Nuclear fission produces radioactive isotopes with decay products encompassing a large proportion of the Periodic Table. Many of these isotopes are considered as waste and are currently disposed of following separation. However, a number of medically useful therapeutic radioisotopes are contained within this waste stream and remain an untapped resource; specifically alpha therapeutic agents such as Ac-225 and Pb-212 (originating from uranium and thorium) which may be used for cancer treatment. Reactor produced radionuclides require rapid and selective separation in a few simple steps before they can undergo bioconjugation to a suitable targeting vector to make them viable as cancer therapeutics. However, the coordination chemistry of these radionuclides differs and achieving direct selective extraction remains challenging. We have recently developed a one pot procedure to selectively extract the long-lived minor actinides from the lanthanides using flexible multidentate polyaminocarboxylate extractants functionalised with amino acids. These are resistant to gamma radiation, operate over a wide pH range,exhibit rapid complexation kinetics; they are easily modified to alter the selectivity for a given metal based on ionic radii and coordination donor preferences.

核裂变产生放射性同位素，其衰变产物包含元素周期表的很大一部分。这些同位素中有许多被认为是废物，目前在分离后被处理掉。然而，这一废物流中含有一些医学上有用的治疗性放射性同位素，仍然是一种未开发的资源；特别是α治疗剂，如Ac-225和Pb-212（源自铀和钍），可用于癌症治疗。反应堆生产的放射性核素需要在几个简单的步骤中进行快速和选择性分离，然后才能与合适的靶向载体进行生物偶联，使其能够作为癌症治疗药物。然而，这些放射性核素的配位化学不同，实现直接选择性提取仍然具有挑战性。我们最近开发了一种用氨基酸功能化的柔性多齿聚氨基羧酸萃取剂从镧系元素中选择性提取长寿命次要锕系元素的一锅方法。这些耐伽马辐射，在广泛的pH范围内操作，表现出快速的络合动力学；根据离子半径和配位给体偏好，它们很容易被修饰以改变对给定金属的选择性。