Radiocopper complexes for imaging & treatment of hypoxic tissues

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.