(Photo: Jan Kilund)

Making nuclear polarization storage possible: new photo-induced non-persistent radical species for dissolution DNP

Andrea Capozzi

Research focus 
The project introduces a paradigm shift in the technique known as dissolution Dynamic Nuclear Polarization (d-DNP) via the development and use of new photo-induced non-persistent radical species.

Owing to its versatility, Nuclear Magnetic Resonance (NMR) spectroscopy arguably is among the most powerful physico-chemical analytical methods with vital contributions to research disciplines as diverse as synthetic chemistry, materials science, clinical imaging, structural biology or metabolism. A principal shortcoming of NMR spectroscopy is its moderate sensitivity. Accordingly, sensitivity improvements instantaneously widen the application range of NMR spectroscopy.

Signal enhancement via d-DNP represents the most efficient and widespread method to dramatically boost the liquid-state NMR sensitivity. This overwhelming liquid-state nuclear polarization enhancement has proven to pave the way for many applications ranging from online enzyme and polymer kinetics to sensitive drug discovery from hyperpolarized (HP) ligand analysis, studies of real-time cell metabolism, and most notably to early clinical cancer diagnosis through HP Magnetic Resonance Imaging (MRI). Dynamic nuclear polarization (DNP) affords breakthroughs in terms of sensitivity by temporarily redistributing nuclear quantum states through coupling to electron magnetic moments by means of microwave irradiation. In principle all kinds of nuclear species can be polarized. Following signal enhancement in the solid-state a fast dissolution with preheated buffer brings the sample into solution. Once the sample has been brought into solution the artificially enhanced signal is available for a few minutes. The latter represents the technique’s main limitation.

It has recently been demonstrated that non-persistent radicals can be used to signal enhance pyruvic acid (PA) and other substrates via d-DNP. Induced upon UV-irradiation of PA molecules at cryogenic temperatures, these radicals are persistent at liquid nitrogen temperature, but are annihilated if the sample temperature increases above 190 K. The focus of this project is to develop new UV-induced non-persistent radical species and take advantage from their thermal instability to circumvent the d-DNP’s main limitation. Mastering the physico-chemical properties of the radicals’ annihilation above a certain temperature, but below the DNP sample’s melting will offer the unique chance to scavenge the radicals in the solid state, after the polarization transfer has been achieved.

The project contributes to the HYPERMAG mission by providing HP substrates free of radicals. The latter can be extracted from the DNP apparatus in the solid form while maintaining the enhanced nuclear polarization. The melting procedure necessary to transform the frozen solid into an HP injectable solution could therefore be performed ex-situ, up to several hours after extraction and storage of the HP solid sample.

Scientific output
Find Andrea's publications at DTU's online research database ORBIT.

Funding
The project is funded by H. C. Ørsted COFUND, a joint program between Marie Skłodowska-Curie Actions (Horizon 2020) and DTU (grant agreement no. 713683 (COFUNDfellowsDTU). The project is part of the HYPERMAG Center of Excellence funded by Danish National Research Foundation (DNRF124).

Project Period
September 2016 - June 2019 

Andrea Capozzi has received a H. C. Ørsted COFUND fellowship grant, co-funded by Marie Skłodowska-Curie Actions 

Contact

Andrea Capozzi
Postdoc
DTU Health Tech
http://www.hypermag.dtu.dk/Research/Postdocs/Andrea-Capozzi
25 SEPTEMBER 2020