Radiocopper complexes for imaging & treatment of hypoxic tissues

用于成像的放射性铜配合物

• 批准号: GR/S60389/02
• 负责人: Philip Blower
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=GR%2FS60389%2F02
• 关键词: Radiocopper; complexes; imaging; treatment; hypoxic

Shortage of oxygen (hypoxia) in tissues occurs in many diseases. It is one of the main causes of cancer treatment failure. A reliable imaging procedure to detect hypoxia, such as PET, would represent a major clinical advance, helping to locate disease within the body, plan treatments, and predict outcomes in oncology, cardiology and neurology. These different clinical contexts will require hypoxia targeting agents tuned to have subtly different in vivo properties, targeting different oxygen levels. In this project we will provide these imaging agents by modifying the prototype agent CuATSM, which is taken up specifically in hypoxic cells, to develop a range of radioactive imaging agents individually optimised for the different uses. We will also develop a new type of treatment for use alongside conventional therapies, in which hypoxia-targeted radioisotopes kill resistant hypoxic cancer cells. To achieve this, a mufti-disciplinary effort is planned at a cost of approximately 300k, to develop production of the radioisotope Cu-64 (radiochemistry, St Thomas' Hospital, London), synthesise a large number of complexes from which to choose those with the best properties (synthetic chemistry, University of Kent), and measure the relevant properties in cultured cancer cells (analytical chemistry and radiobiology, University of Kent). The new products will be tested in vivo by collaboration with groups at Royal Free Hospital. London. and Washington University. St. Louis. USA.

组织中的氧缺乏（缺氧）发生在许多疾病中。它是癌症治疗失败的主要原因之一。一个可靠的成像程序来检测缺氧，如PET，将代表一个重大的临床进步，有助于定位体内疾病，计划治疗，并预测肿瘤学，心脏病学和神经病学的结果。这些不同的临床背景将需要调整低氧靶向剂以具有微妙不同的体内性质，靶向不同的氧水平。在这个项目中，我们将通过修改原型药物CuATSM来提供这些成像剂，该原型药物专门用于缺氧细胞，以开发一系列针对不同用途单独优化的放射性成像剂。我们还将开发一种与传统疗法一起使用的新型治疗方法，其中低氧靶向放射性同位素杀死耐缺氧癌细胞。为了实现这一目标，计划花费约30万美元进行多学科努力，以开发放射性同位素Cu-64的生产（放射化学，圣托马斯医院，伦敦），合成大量的络合物，从中选择具有最佳性能的那些（合成化学，肯特大学），并测量培养的癌细胞中的相关性质（分析化学和放射生物学，肯特大学）。新产品将通过与皇家自由医院的小组合作进行体内测试。伦敦。和华盛顿大学。圣路易斯USA.