Stable electron-irradiated [1- 13 C]alanine radicals for metabolic imaging with dynamic nuclear polarization

Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance experiments by >10 4 -fold, permitting isotopically labeled molecules to be transiently visible in magnetic resonance imaging scans. dDNP mechanistically takes place at ~1 K and requires unpaired elect...

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Veröffentlicht in:	Science advances Jg. 11; H. 47; S. eadz4334
Hauptverfasser:	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, Myers, William, Richardson, Zoe, Lewis, Jarrod, Kennedy, Brett W. C., Bowen, Alice M., Bertelsen, Lotte Bonde, Laustsen, Christoffer, Tyler, Damian J., Miller, Jack J.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 21.11.2025
Schlagworte:	Alanine - chemistry Alanine - metabolism Animals Carbon Isotopes - chemistry Electrons Free Radicals - chemistry Kidney - diagnostic imaging Kidney - metabolism Magnetic Resonance Imaging - methods Rats
ISSN:	2375-2548, 2375-2548
Online-Zugang:	Volltext
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Abstract	Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance experiments by >10 4 -fold, permitting isotopically labeled molecules to be transiently visible in magnetic resonance imaging scans. dDNP mechanistically takes place at ~1 K and requires unpaired electrons and microwaves. These electrons are usually chemical radicals, requiring removal by filtration prior to injection into humans. Alternative sources, such as ultraviolet irradiation, generate lower polarization and require cryogenic transport. We present ultrahigh–dose rate electron irradiation as an alternative for generating nonpersistent 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 polarization (17%) to trityl radicals used clinically (19%) through a previously unknown mechanism we believe to involve partial ordering and electron-electron interactions. Owing to the large radiation doses required, this process is sterilizing, permits imaging of alanine metabolism in vivo in the rat kidney, and may aid clinically translating dDNP. Six-MeV electrons generate stable radicals for more accessible metabolic imaging with dDNP through a previously unknown mechanism.
AbstractList	Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance experiments by >10 4 -fold, permitting isotopically labeled molecules to be transiently visible in magnetic resonance imaging scans. dDNP mechanistically takes place at ~1 K and requires unpaired electrons and microwaves. These electrons are usually chemical radicals, requiring removal by filtration prior to injection into humans. Alternative sources, such as ultraviolet irradiation, generate lower polarization and require cryogenic transport. We present ultrahigh–dose rate electron irradiation as an alternative for generating nonpersistent 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 polarization (17%) to trityl radicals used clinically (19%) through a previously unknown mechanism we believe to involve partial ordering and electron-electron interactions. Owing to the large radiation doses required, this process is sterilizing, permits imaging of alanine metabolism in vivo in the rat kidney, and may aid clinically translating dDNP. Six-MeV electrons generate stable radicals for more accessible metabolic imaging with dDNP through a previously unknown mechanism. Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance experiments by >10 -fold, permitting isotopically labeled molecules to be transiently visible in magnetic resonance imaging scans. dDNP mechanistically takes place at ~1 K and requires unpaired electrons and microwaves. These electrons are usually chemical radicals, requiring removal by filtration prior to injection into humans. Alternative sources, such as ultraviolet irradiation, generate lower polarization and require cryogenic transport. We present ultrahigh-dose rate electron irradiation as an alternative for generating nonpersistent 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 polarization (17%) to trityl radicals used clinically (19%) through a previously unknown mechanism we believe to involve partial ordering and electron-electron interactions. Owing to the large radiation doses required, this process is sterilizing, permits imaging of alanine metabolism in vivo in the rat kidney, and may aid clinically translating dDNP.
Author	Lau, Justin Y. C. Rooney, Catriona H. E. Petersson, Kristoffer Hansen, Esben S. S. Kennedy, Brett W. C. Smart, Sean Bowen, Alice M. Christensen, Nichlas Vous Myers, William Dang, Duy A. Miller, Jack J. Richardson, Zoe Tullis, Iain D. C. Vojnovic, Borivoj Laustsen, Christoffer Bertelsen, Lotte Bonde Tyler, Damian J. Lewis, Jarrod
Author_xml	– sequence: 1 givenname: Catriona H. E. orcidid: 0000-0003-4973-3347 surname: Rooney fullname: Rooney, Catriona H. E. – sequence: 2 givenname: Justin Y. C. orcidid: 0000-0001-7316-811X surname: Lau fullname: Lau, Justin Y. C. – sequence: 3 givenname: Esben S. S. orcidid: 0000-0001-5512-9870 surname: Hansen fullname: Hansen, Esben S. S. – sequence: 4 givenname: Nichlas Vous orcidid: 0000-0001-7390-6071 surname: Christensen fullname: Christensen, Nichlas Vous – sequence: 5 givenname: Duy A. orcidid: 0009-0003-4508-2249 surname: Dang fullname: Dang, Duy A. – sequence: 6 givenname: Kristoffer orcidid: 0000-0003-0300-5790 surname: Petersson fullname: Petersson, Kristoffer – sequence: 7 givenname: Iain D. C. orcidid: 0000-0001-5148-0161 surname: Tullis fullname: Tullis, Iain D. C. – sequence: 8 givenname: Borivoj surname: Vojnovic fullname: Vojnovic, Borivoj – sequence: 9 givenname: Sean orcidid: 0000-0002-0919-4505 surname: Smart fullname: Smart, Sean – sequence: 10 givenname: William orcidid: 0000-0001-5935-9112 surname: Myers fullname: Myers, William – sequence: 11 givenname: Zoe orcidid: 0009-0008-3612-2401 surname: Richardson fullname: Richardson, Zoe – sequence: 12 givenname: Jarrod orcidid: 0000-0001-7838-4241 surname: Lewis fullname: Lewis, Jarrod – sequence: 13 givenname: Brett W. C. orcidid: 0000-0003-4143-3729 surname: Kennedy fullname: Kennedy, Brett W. C. – sequence: 14 givenname: Alice M. orcidid: 0000-0002-6413-2841 surname: Bowen fullname: Bowen, Alice M. – sequence: 15 givenname: Lotte Bonde orcidid: 0000-0002-2491-3184 surname: Bertelsen fullname: Bertelsen, Lotte Bonde – sequence: 16 givenname: Christoffer orcidid: 0000-0002-0317-2911 surname: Laustsen fullname: Laustsen, Christoffer – sequence: 17 givenname: Damian J. orcidid: 0000-0002-0780-8905 surname: Tyler fullname: Tyler, Damian J. – sequence: 18 givenname: Jack J. orcidid: 0000-0002-6258-1299 surname: Miller fullname: Miller, Jack J.
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Snippet	Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance experiments by >10 4 -fold, permitting isotopically labeled... Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance experiments by >10 -fold, permitting isotopically labeled...
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SubjectTerms	Alanine - chemistry Alanine - metabolism Animals Carbon Isotopes - chemistry Electrons Free Radicals - chemistry Kidney - diagnostic imaging Kidney - metabolism Magnetic Resonance Imaging - methods Rats
Title	Stable electron-irradiated [1- 13 C]alanine radicals for metabolic imaging with dynamic nuclear polarization
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