Hyperpolarized ultra-low field (ULF) magnetic resonance to design next generation functional contrast agents

Informations projet

HyperULFNMR

N° de convention de subvention: 949180

DOI

10.3030/949180

Projet clôturé

Date de signature de la CE 29 Juillet 2020

Date de début 1 Janvier 2021

Date de fin 31 Decembre 2025

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 500 000,00

Contribution de l’UE

€ 1 500 000,00

Coordonné par

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany

Periodic Reporting for period 4 - HyperULFNMR (Hyperpolarized ultra-low field (ULF) magnetic resonance to design next generation functional contrast agents)

Période du rapport: 2025-07-01 au 2025-12-31

Résumé du contexte et des objectifs généraux du projet

Cancer is one of the leading causes of death in our society. New methods to diagnose and to assess treatment promise to benefits patients health and increase life expectancy. Magnetic resonance imaging (MRI) is a powerful technique used in hospitals all over the world to assess cancer. Although it is a widespread technique it is inherently insensitive. To circumvent this, hyperpolarization approaches have been devised to boost magnetic resonance signals by several orders of magnitude. Hyperpolarization has been shown to allow for the enhancement of metabolites that can then directly be used to monitor biochemical conversion in vivo in real-time with the hope to improve cancer imaging. The proposed research aims at developing new contrast agents that can be hyperpolarized and particular be used in portable magnetic resonance devices. This would improve access to MRI on the world for new cancer screenings and early diagnosis. Ultimately, this will benefit patients all around the world. The overall objective of the project is to discover suitable molecules that extend the capabilities of hyperpolarized magnetic resonance in particular for the use in portable low field devices.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Since the beginning of the project a variety of molecules have been synthesized that are metabolically active and could be hyperpolarize with a rapid approach using a special form of hydrogen in less than one minute. The state-of-the-art technology requires 10s of minutes to hours for a similar process. In particular, we focused on investigating cancer cells at first to show that the obtained hyperpolarized compounds are converted into the downstream metabolites. In a next step we could show that the technology is even applicable for tumor imaging and to monitor metabolism in brain and liver. In the second part of the project time we finalized the construction of a low field devices that is portable and has a field strength of typical kitchen/refrigerator magnets. We could show that in such low magnetic fields metabolic experiments with cancer cells are possible. The results were disseminated in scientific journals and as part of scientific presentations. The work achieved further awareness by the Felix Bloch Award of the German Chemical Society that was awarded to the PI in 2021.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

We progressed beyond the stat-of-the-art in several ways: 1) New molecules were synthesized that enable an efficient hyperpolarization of many metabolites and enabled the first metabolic tumor imaging experiments using parahydrogen as a hyperpolarization source. 2) Molecule concepts were introduced showing that 15N enriched molecular probes can be created and hyperpolarized with parahydrogen that are responsive to reactive oxygen species (ROS) . ROS are a hallmark of cancer and are relevant in cancer treatment strategies. 3) We could show that hyperpolarized molecules can be used to probe transient metabolic species that were unobservable otherwise. More precisely, we could detect and assign a reaction intermediate of pyruvate with the ROS hydrogen peroxide, which was so far not detected in solution. This proofs a mechanism on how pyruvate can act as a cell protectant.