Radiocopper complexes for imaging & treatment of hypoxic tissues

许多疾病都会出现组织中的缺氧现象。它是癌症治疗失败的主要原因之一。一种可靠的检测缺氧的成像程序，如PET，将代表着临床的重大进步，有助于定位体内的疾病，计划治疗，并预测肿瘤学、心脏病学和神经学的结果。这些不同的临床情况将需要低氧靶向试剂调整为具有微妙不同的体内特性，针对不同的氧气水平。在这个项目中，我们将通过修改原型试剂CuATSM来提供这些显像剂，CuATSM是专门在低氧细胞中使用的，以开发一系列针对不同用途而单独优化的放射性显像剂。我们还将开发一种与传统疗法一起使用的新型疗法，在这种疗法中，低氧靶向的放射性同位素杀死耐药的低氧癌细胞。为了实现这一目标，计划耗资约300k的多学科努力，以开发放射性同位素铜-的生产(放射化学，伦敦圣托马斯医院)，合成大量的络合物以从中选择那些具有最好性能的络合物(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在体内进行测试。伦敦。和华盛顿大学。圣路易斯。美国。

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.