Stable electron-irradiated [1-$^{13}$C]alanine radicals for clinically viable metabolic imaging with Dynamic Nuclear Polarization

Fuente: arXiv
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Autori principali: Rooney, Catriona H. E., Lau, Justin Y. C., Hansen, Esben S. S., Christensen, Nichlas Vous, Dang, Duy A., Petersson, Kristoffer, Tullis, Iain D. C., Vojnovic, Borivoj, Smart, Sean, Lewis, Jarrod, Myers, William, Richardson, Zoe, Kennedy, Brett W. C., Bowen, Alice M., Bertelsen, Lotte Bonde, Laustsen, Christoffer, Tyler, Damian J., Miller, Jack J.
Natura: Preprint
Pubblicazione: 2025
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author Rooney, Catriona H. E.
Lau, Justin Y. C.
Hansen, Esben S. S.
Christensen, Nichlas Vous
Dang, Duy A.
Petersson, Kristoffer
Tullis, Iain D. C.
Vojnovic, Borivoj
Smart, Sean
Lewis, Jarrod
Myers, William
Richardson, Zoe
Kennedy, Brett W. C.
Bowen, Alice M.
Bertelsen, Lotte Bonde
Laustsen, Christoffer
Tyler, Damian J.
Miller, Jack J.
author_facet Rooney, Catriona H. E.
Lau, Justin Y. C.
Hansen, Esben S. S.
Christensen, Nichlas Vous
Dang, Duy A.
Petersson, Kristoffer
Tullis, Iain D. C.
Vojnovic, Borivoj
Smart, Sean
Lewis, Jarrod
Myers, William
Richardson, Zoe
Kennedy, Brett W. C.
Bowen, Alice M.
Bertelsen, Lotte Bonde
Laustsen, Christoffer
Tyler, Damian J.
Miller, Jack J.
contents Dissolution Dynamic Nuclear Polarisation (dDNP) increases the sensitivity of magnetic resonance experiments by $>10^4$-fold, permitting isotopically-labelled molecules to be transiently visible in MRI scans. dDNP requires a source of unpaired electrons in contact with labelled nuclei, cooled to $\sim$1K, and spin-pumped into a given state by microwaves. These electrons are usually chemical radicals, requiring removal by filtration prior to injection into humans. Alternative sources, such as UV irradiation, generate lower polarisation and require cryogenic transport. We present ultra-high-dose-rate electron irradiation as a novel alternative for generating non-persistent radicals in alanine/glycerol mixtures. These are stable for months at room temperature, quench spontaneously upon dissolution, are present in dose-dependent concentrations, and generate comparable nuclear polarisation to trityl radicals used clinically (20\%) through a novel mechanism. This process is inherently sterilising, permitting imaging of alanine metabolism \textit{in vivo}. As well as scientific novelty, this overcomes the biggest barrier to clinically translating dDNP.
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id arxiv_https___arxiv_org_abs_2504_16621
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Stable electron-irradiated [1-$^{13}$C]alanine radicals for clinically viable metabolic imaging with Dynamic Nuclear Polarization
Rooney, Catriona H. E.
Lau, Justin Y. C.
Hansen, Esben S. S.
Christensen, Nichlas Vous
Dang, Duy A.
Petersson, Kristoffer
Tullis, Iain D. C.
Vojnovic, Borivoj
Smart, Sean
Lewis, Jarrod
Myers, William
Richardson, Zoe
Kennedy, Brett W. C.
Bowen, Alice M.
Bertelsen, Lotte Bonde
Laustsen, Christoffer
Tyler, Damian J.
Miller, Jack J.
Medical Physics
Biomolecules
Dissolution Dynamic Nuclear Polarisation (dDNP) increases the sensitivity of magnetic resonance experiments by $>10^4$-fold, permitting isotopically-labelled molecules to be transiently visible in MRI scans. dDNP requires a source of unpaired electrons in contact with labelled nuclei, cooled to $\sim$1K, and spin-pumped into a given state by microwaves. These electrons are usually chemical radicals, requiring removal by filtration prior to injection into humans. Alternative sources, such as UV irradiation, generate lower polarisation and require cryogenic transport. We present ultra-high-dose-rate electron irradiation as a novel alternative for generating non-persistent radicals in alanine/glycerol mixtures. These are stable for months at room temperature, quench spontaneously upon dissolution, are present in dose-dependent concentrations, and generate comparable nuclear polarisation to trityl radicals used clinically (20\%) through a novel mechanism. This process is inherently sterilising, permitting imaging of alanine metabolism \textit{in vivo}. As well as scientific novelty, this overcomes the biggest barrier to clinically translating dDNP.
title Stable electron-irradiated [1-$^{13}$C]alanine radicals for clinically viable metabolic imaging with Dynamic Nuclear Polarization
topic Medical Physics
Biomolecules
url https://arxiv.org/abs/2504.16621