Ultra-high dose rate 6 MeV electron irradiation generates stable [1-$^{13}$C]alanine radicals suitable for medical imaging with dissolution Dynamic Nuclear Polarisation
Ultra-high dose rate 6 MeV electron irradiation generates stable [1-$^{13}$C]alanine radicals suitable for medical imaging with dissolution Dynamic Nuclear Polarisation
Dissolution Dynamic Nuclear Polarisation (dDNP) is an experimental technique that increases the sensitivity of magnetic resonance experiments by more than a factor of $10^5$, permitting isotopically-labelled molecules to be transiently visible in MRI scans with their biochemical fates spatially resolvable over time following injection into a patient. dDNP requires a source of unpaired electrons to be in contact with the isotope-labelled nuclei, cooled to temperatures close to absolute zero, and spin-pumped into a given state by microwave irradiation. At present, these electrons are typically provided by chemical radicals which require removal by filtration prior to injection into humans. Alternative sources include UV irradiation, requiring storing samples in liquid nitrogen, or cobalt-60 gamma irradiation, which requires days and generates polarisation two to three orders of magnitude lower than chemical radicals. In this study, we present ultra-high dose rate electron beam irradiation as a novel alternative for generating non-persistent radicals in glycerol/alanine mixtures. These radicals are stable for months at room temperature, are present at concentrations dependent on irradiation dose, and generate comparable nuclear polarisation to the typically used trityl radicals (20%) through a novel mechanism. The process of their generation inherently sterilises samples, and they enable the imaging of alanine metabolism in vivo using dDNP. This new method of generating radicals for dDNP offers the potential to report on relevant biological processes while being translatable to the clinic.
Catriona H. E. Rooney、Justin Y. C. Lau、Esben S. S. Hansen、Nichlas Vous Christensen、Duy A. Dang、Kristoffer Petersson、Iain Tullis、Borivoj Vojnovic、Sean Smart、Jarrod Lewis、William Myers、Zoe Richardson、Brett W. C. Kennedy、Alice M. Bowen、Lotte Bonde Bertelsen、Christoffer Laustsen、Damian J. Tyler、Jack J. Miller
Department of Physiology, Anatomy and Genetics, University of OxfordGE HealthCare, Waukesha, WI, USAThe MR Research Centre, Aarhus University, Aarhus, DenmarkThe MR Research Centre, Aarhus University, Aarhus, DenmarkThe MR Research Centre, Aarhus University, Aarhus, DenmarkDepartment of Oncology, University of OxfordDepartment of Oncology, University of OxfordDepartment of Oncology, University of OxfordDepartment of Oncology, University of OxfordDepartment of Material Science, University of OxfordCAESR, Department of Chemistry, University of OxfordDepartment of Physics, University of OxfordDepartment of Physiology, Anatomy and Genetics, University of OxfordDepartment of Material Science, University of OxfordThe MR Research Centre, Aarhus University, Aarhus, DenmarkThe MR Research Centre, Aarhus University, Aarhus, DenmarkDepartment of Physiology, Anatomy and Genetics, University of OxfordThe MR Research Centre, Aarhus University, Aarhus, Denmark
医学研究方法
Catriona H. E. Rooney,Justin Y. C. Lau,Esben S. S. Hansen,Nichlas Vous Christensen,Duy A. Dang,Kristoffer Petersson,Iain Tullis,Borivoj Vojnovic,Sean Smart,Jarrod Lewis,William Myers,Zoe Richardson,Brett W. C. Kennedy,Alice M. Bowen,Lotte Bonde Bertelsen,Christoffer Laustsen,Damian J. Tyler,Jack J. Miller.Ultra-high dose rate 6 MeV electron irradiation generates stable [1-$^{13}$C]alanine radicals suitable for medical imaging with dissolution Dynamic Nuclear Polarisation[EB/OL].(2025-04-23)[2025-05-13].https://arxiv.org/abs/2504.16621.点此复制
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