Nuclear spin singlet states in self-assembling nanostructures as contrast agents for magnetic resonance imaging.

点击翻译按钮获取中文摘要

The phenomenon of nuclear magnetic resonance (NMR) and the possibilities to utilize it for imaging has lead to better medicaldiagnostics and monitoring of diseases. A crucial aspect is the utilization of contrast agents that allow for the better localization ofillnesses. Typical contrast agents thereby consist out of transition metal complexes which have partly been identified in recent years tobe neurotoxic. The development of alternative molecules for better diagnostics in the future is therefor highly desirable. In this proposal, I am planning to utilize the phenomenon of nuclear spin singlet states as contrast mechanism and to develop self-assembling moleculesthat react upon the presence of glutathione. Glutathione is an antioxidant present in high concentrations in many cancer cells.Nuclear spin singlet states are not observable with NMR but can be probed indirectly. The special feature of these states is that theequilibration with the thermodynamical favored triplet state is often very long. This time can be up to two orders of magnitude longer than the longitudinal relaxation time, a measure of molecular dynamics.Due to this long lifetime novel possibilities emerge to investigate dynamic effects and to specifically utilize this effect to design molecules that act as contrast agents. We are going to use this phenomenon to develop self-assembling molecules that can be imaged via a novel NMR methodology proposed here. At first, the molecules will be dissolved and the self-assembling process to nanoparticles triggered by chemical reduction with glutathione. The singlet lifetime will be different in the dissolved and the assembled state leading to a new contrast mechanism to detect glutathione. In addition to the development of molecular systems, I am planning to advance the NMR methodology. In particular, I am proposing a NMR experiment that enhances the detectable signal of the newly synthesized contrast agents in spectroscopic and imaging experiments. In the last step all of the above will be combined to demonstrate that glutathione can be detected in cells with the proposed approach.