Enhancing MR-Sensitivity of 19F-biomarkers and PET-analogous 19F-labeled receptor ligands by parahydrogen-induced polarization

• Applicant: Professor Dr. Johannes Bernarding
• Subject Area: Analytical Chemistry ; Medical Physics, Biomedical Technology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257631981

PET is the gold standard of molecular imaging for example to label cellular receptors in Alzheimer research. PET is highly sensitive (nmol - pmol) but requires a very expensive infrastructure (on-site generation of radioactive markers, PET-scanner) and exhibits only a moderate spatial resolution. Standard MR methods do not represent an alternative option as the NMR-sensitivity is orders of magnitude smaller. However, hyperpolarization (HP) techniques can enhance NMR-signals by a factor of up to 10000. First applications demonstrate a high potential of those methods in medical fields: dynamic nuclear polarization (DNP) is applied in a first clinical study (with 13C), PHIP und DNP are used for spectroscopy of cellular metabolites, hyperpolarized noble gases are applied in lung imaging and chemical exchange saturation transfer (Hyper-CEST) experiments, and hyperpolarized 13C is used to investigate receptor binding to lipids. Recently, pyridine and nicotine were hyperpolarized without incorporation of hydrogen (SABRE). This new method allowed detection of nmol concentrations. Nicotine and pyridine are fundamental substructures of PET-markers for nicotinic acetylcholine receptors (nAChR). Until now, it was not yet investigated whether the sensitivity of PET-analogous hyperpolarized MR-substrates allows to analyze the binding processes on according receptors. Thus the working program of the proposal focuses on basic research and the feasibility of this approach. In addition to further optimize and investigate the 19F-markers of our previous project new issues will be addressed: a) development of water-soluble catalysts for SABRE, b) investigation of the 1H, 19F, 13C and 15N signal enhancement by SABRE in PET-analogous markers and of potential signal changes after binding to model systems, c) bio¬compatibility of the developed solutions. In the past funding period the technical infrastructure was established, new substrate classes were hyperpolarized, and the first images of 19F-hyperpolarized substrates were measured. The simultaneous detection of 1H and 19F signals of hyper¬polarized compounds was also realized at low magnetic fields. Continuing the productive cooperation with the working groups of Buntkowsky and Bommerich this project will elucidate in which applications protein-ligand-systems can be detected with high spatial resolution using PHIP-methods.Summarizing, the main goal of the project is the analysis whether the potential of selective binding of hyperpolarized PET-analogous marker molecules to relevant cellular receptors (i.e. nAChR) can potentially be used in NMR and MRI in analogy to PET. As a PET-MR will be soon installed in Magdeburg the proposed work will provide the necessary base for future work compromising a direct comparison of the sensitivity of PET and PET-analogous MR markers.

• DFG Programme: Research Grants
• Participating Persons: Professor Dr. Joachim Bargon; Professor Dr. Gerd Buntkowsky