Optimierungen von Hyperpolarisationsmethoden basierend auf para-Wasserstoff hinsichtlich ihrer Biokompatibilität für in-vivo-Anwendungen in der Kernspinresonanz
- Optimization of hyperpolarization methods based on parahydrogen regarding their biocompatibility for in vivo applications in nuclear magnetic resonance
Emondts, Meike; Blümich, Bernhard (Thesis advisor); Klankermayer, Jürgen (Thesis advisor)
Dissertation / PhD Thesis
Dissertation, RWTH Aachen University, 2017
The combination of hyperpolarization methods and imaging enables the detection of heteronuclei and opens up innovative fields of application in medical diagnostics. The fascinating properties, such as almost background-free signaling and large chemical shifting differences, which allow the tracking of chemical changes of low-concentrated biomarkers, can provide detailed insight into biochemical processes at the molecular level. The hyperpolarization methods based on parahydrogen (p-H2) have the potential for a wide application as they are simple, cost-effective and fast. However, the biocompatibility in combination with high polarization efficiency is a major challenge. The aim of the work was to optimize the PHIP methods with regard to these points.In the first part, a basis for a proper characterization of PHIP systems was established. A method based on kinetic studies has been developed that allows the determination of the polarization transfer efficiency (PTE) in PHIP experiments. This method was then applied to study homogeneous catalysts to investigate the influence of the chemical system. It was found that the T1 time as well as the lifetime and the concentration of the intermediates decisively influence the PTE. The PTE is a precise parameter which properly characterizes the chemical PHIP system, thus enabling comparison and optimization of known systems as well as the development of new systems. Furthermore, for the first time, PHIP was demonstrated with the help of a novel, artificial metalloenzyme consisting of a Rhodium triphos catalyst covalently bound to a biomolecular framework. The polarization efficiency is exceptionally high compared to other systems. The metalloenzyme is an innovative immobilization method for PHIP catalysts and is ideally suited for biomedical applications due to the activity in water, the easy separability and the high polarization efficiency.In the next chapter, the water-soluble catalyst precursor [Ir(IDEG)(COD)Cl] was used to demonstrate SABRE in a pure water system for the first time. Here, the polarization could be transferred to both protons and 15N nuclei of biomarker molecules, such as diazirine and nicotinamide. The hyperpolarization in pure water without the use of toxic solvents opens the door to the biomedical application of SABRE.The last chapter deals with the polarization of solvents. For the first time, water could be hyperpolarized by means of p-H2 in the presence of [Ir(IDEG)(COD)Cl] and histidine. The polarization of solvent protons can be transferred to heteronuclei of biomedical relevant molecules that are not polarizable by the typical SABRE mechanism.In summary, the hyperpolarization methods based on p-H2 could be significantly optimized with regard to their biocompatibility and thus great steps towards biomedical application could be achieved.