Artificial Siderophores for molecular imaging applications

Iron is an essential element for almost all living organisms for a variety of biological function. As soluble iron has a very limited availability, microorganisms such as bacteria and fungi have developed over the course of evolution so called siderophores (Greek: iron carrier), that they secrete into their environment to scavenge the rare iron. They then specifically take up siderophore-bound iron via dedicated transport mechanisms. This provides microorganisms with a competitive advantage over organisms that lack siderophores, including human cells. Therefore, siderophores play an important role for bacterial and fungal pathogens during human infections. Siderophores have been widely investigated in biomedical research with desferrioxamine B (DFOB) being the most successfully used, available as a drug called Desferal to treat patients with iron overload. In this SideroArt project synthetically produced (artificial) siderophores, mimicking their biological function will be developed and investigated for their use as molecular imaging agents for medical diagnosis. By replacing iron by radioactive atoms such as Gallium-68 or Zirkonium-89, it is possible to use the emitted radiation to generate an image by means of Positron emission tomography (PET) to detect infections due to accumulation of the siderophore by pathogens. By a synthetic design, siderophores will be chemically modified to change and optimize their properties. This also allows further applications towards other imaging methods and even treatment of infections. The project is a cooperation with the University of Wrozlaw (E. Gumienna-Kontecka and E. Wojaczynska), where novel siderophores are designed and synthesized, the Medical University Innsbruck, where these compounds will be radiolabelled and characterized towards their ability to be taken up by microorganisms (C. Decristoforo, H. Haas) and the University of Olomouc (M. Petrik), where imaging studies are performed to evaluate the infection imaging properties and prove the proposed concept. This project holds the potential for the development of new methods for early and highly accurate detection of infections, as well as for opening new possibilities for treating patients with infections.