Platform technology to create long-lasting hyperpolarization on PHIP-labeled, targeting DNA aptamers

• Applicant: Dr. Meike Emondts
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 532913673

Targeted imaging offers a powerful diagnostic tool in the field of personalized medicine and enables early detection and identification of disease sites. Magnetic resonance imaging (MRI) offers an excellent imaging modality due to its high spatial resolution and the non-invasive and non-radiative character. However, especially in molecular imaging, the low sensitivity is a limiting factor. Hyperpolarization methods offer the possibility to amplify MR signals by several orders of magnitude. For hyperpolarized MRI, small molecules/metabolites are mainly used to monitor metabolism in real time, whereas there are only few studies on hyperpolarization of targeted contrast agents. These usually consist of a unit with targeting properties and an imaging marker. Here, DNA aptamers offer excellent properties as targeting units; they consist of short strands of DNA and can be engineered to bind to a desired target (e.g. a pathogenic site) with high affinity and selectivity. The goal of this project is the development of a platform technology for the hyperpolarization of PHIP-labeled DNA aptamers as novel contrast agents for targeted MRI. For that, we will first develop suitable, universal PHIP markers that can be incorporated into any type of DNA aptamer and can be hyperpolarized with great efficiency and a long lifetime. Second, these labels will be incorporated into DNA and experimental conditions will be optimized with the aim of achieving molar polarization levels and lifetimes suitable for future in vivo applications (c = 50 mM, T > 1-2 min.). Finally, we will separate the hyperpolarized DNA from the toxic reaction medium by precipitation methods to obtain a purified compound. Hyperpolarized, targeted imaging will not only significantly increase the sensitivity of established MR systems, but especially in combination with (ultra-)low-field MRI, new diagnostic and analytic avenues may open up in the future.

• DFG Programme: Research Grants
• International Connection: Spain
• Co-Investigators: Dr. Jens Köhler; Dr. Rostislav Vinokur
• Cooperation Partner: Dr. James Eills