8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Synthesis and evaluation of 13C-labeled 5-5-dimethyl-1-pyrroline-N-oxide aimed at in vivo detection of reactive oxygen species using hyperpolarized 13C-MRI

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Effective means to identify the role of reactive oxygen species (ROS) mediating several diseases including cancer, ischemic heart disease, stroke, Alzheimer’s and other inflammatory conditions in in vivo models would be useful. The cyclic nitrone 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) is a spin trap frequently used to detect free radicals in vitro using Electron Paramagnetic Resonance (EPR) spectroscopy. In this study, we synthesized 13C-labeled DMPO for hyperpolarization by dynamic nuclear polarization, in which 13C NMR signal increases more than 10000-fold. This allows in vivo 13C MRI to investigate the feasibility of in vivo ROS detection by the 13C-MRI. DMPO was 13C-labeled at C5 position, and deuterated to prolong the T 1 relaxation time. The overall yield achieved for 5- 13C-DMPO-d 9 was 15%. Hyperpolarized 5- 13C-DMPO-d provided a single peak at 76 ppm in the 13C-spectrum, and the T 1 was 60 s in phosphate buffer making it optimal for in vivo 13C MRI. The buffered solution of hyperpolarized 5- 13C-DMPO-d 9 was injected into a mouse placed in a 3 T scanner, and 13C-spectra were acquired every 1 s. In vivo studies showed the signal of 5- 13C-DMPO-d 9 was detected in the mouse, and the T 1 decay of 13C signal of hyperpolarized 5- 13C-DMPO-d 9 was 29 s. 13C-chemical shift imaging revealed that 5- 13C-DMPO-d 9 was distributed throughout the body in a minute after the intravenous injection. A strong signal of 5- 13C-DMPO-d 9 was detected in heart/lung and kidney, whereas the signal in liver was small compared to other organs. The results indicate hyperpolarized 5- 13C-DMPO-d 9 provided sufficient 13C signal to be detected in the mouse in several organs, and can be used to detect ROS in vivo.

          Graphical Abstract:

          Related collections

          Author and article information

          Journal
          8709159
          3902
          Free Radic Biol Med
          Free Radic. Biol. Med.
          Free radical biology & medicine
          0891-5849
          1873-4596
          3 December 2018
          22 November 2018
          01 February 2019
          01 February 2020
          : 131
          : 18-26
          Affiliations
          [a ]Radiation Biology Branch, National Cancer Institute, Bethesda, MD, USA
          [b ]Imaging Probe Development Center, National Heart, Lung, and Blood Institute, Rockville, MD, USA
          [c ]Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Hokkaido, Japan
          Author notes
          [* ]Corresponding author: Murali C. Krishna, Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room B3B69, NIH, 9000 Rockville Pike, Bethesda, MD 20892-1002. Phone: 301-496-7511; Fax: 301-480-2238 murali@ 123456helix.nih.gov.
          Article
          PMC6983923 PMC6983923 6983923 nihpa1515727
          10.1016/j.freeradbiomed.2018.11.013
          6983923
          30471347
          78b7bb0d-225c-4694-89d5-2b8f66ee56cd
          History
          Categories
          Article

          DMPO: reactive oxygen species,hyperpolarized 13C-MRI,spin trapping

          Comments

          Comment on this article