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DOI10.1073/pnas.2014631118
Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging
Hesse F.; Somai V.; Kreis F.; Bulat F.; Wright A.J.; Brindle K.M.
发表日期2021
ISSN00278424
卷号118期号:12
英文摘要2H magnetic resonance spectroscopic imaging has been shown recently to be a viable technique for metabolic imaging in the clinic. We show here that 2H MR spectroscopy and spectroscopic imaging measurements of [2,3-2H2]malate production from [2,3-2H2]fuma-rate can be used to detect tumor cell death in vivo via the production of labeled malate. Production of [2,3-2H2]malate, following injection of [2,3-2H2]fumarate (1 g/kg) into tumor-bearing mice, was measured in a murine lymphoma (EL4) treated with etoposide, and in human breast (MDA-MB-231) and colorectal (Colo205) xenografts treated with a TRAILR2 agonist, using surface-coil localized 2H MR spectroscopy at 7 T. Malate production was also imaged in EL4 tumors using a fast 2H chemical shift imaging sequence. The malate/fumarate ratio increased from 0.016 ± 0.02 to 0.16 ± 0.14 in EL4 tumors 48 h after drug treatment (P = 0.0024, n = 3), and from 0.019 ± 0.03 to 0.25 ± 0.23 in MDA-MB-231 tumors (P = 0.0001, n = 5) and from 0.016 ± 0.04 to 0.28 ± 0.26 in Colo205 tumors (P = 0.0002, n = 5) 24 h after drug treatment. These increases were correlated with increased levels of cell death measured in excised tumor sections obtained immediately after imaging. 2H MR measurements of [2,3-2H2]malate production from [2,3-2H2]fumarate provide a potentially less expensive and more sensitive method for detecting cell death in vivo than 13C MR measurements of hyperpolarized [1,4-13C2]fumarate metabolism, which have been used previously for this purpose. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Cell death | tumor | MRI | deuterium
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180176
作者单位Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, United Kingdom; Department of Radiology, School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0SL, United Kingdom; Department of Information Technology and Electrical Engineering, ETH Zürich, Zürich, 8092, Switzerland; Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom; Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, United Kingdom
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Hesse F.,Somai V.,Kreis F.,et al. Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging[J],2021,118(12).
APA Hesse F.,Somai V.,Kreis F.,Bulat F.,Wright A.J.,&Brindle K.M..(2021).Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA Hesse F.,et al."Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).
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