Harue Kubota1, Denis A Komarov1, Hironobu Yasui2, Shingo Matsumoto1, Osamu Inanami3, Igor A Kirilyuk4, Valery V Khramtsov5, Hiroshi Hirata6. 1. Division of Bioengineering and Bioinformatics, Graduate School of Information Science and Technology, Hokkaido University, North 14, West 9, Kita-ku, Sapporo, 060-0814, Japan. 2. Central Institute of Isotope Science, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-0815, Japan. 3. Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido University, North 18, West 9, Kita-ku, Sapporo, 060-0818, Japan. 4. N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, 9, Ac. Lavrentieva Ave., Novosibirsk, 630090, Russia. 5. Department of Biochemistry, West Virginia University, Robert C. Byrd Health Sciences Center, 1 Medical Center Drive, Morgantown, WV, 26506, USA. 6. Division of Bioengineering and Bioinformatics, Graduate School of Information Science and Technology, Hokkaido University, North 14, West 9, Kita-ku, Sapporo, 060-0814, Japan. hhirata@ist.hokudai.ac.jp.
Abstract
OBJECTIVES: The aim of this study was to demonstrate the feasibility of in vivo three-dimensional (3D) relaxation time T 2* mapping of a dicarboxy-PROXYL radical using continuous-wave electron paramagnetic resonance (CW-EPR) imaging. MATERIALS AND METHODS: Isotopically substituted dicarboxy-PROXYL radicals, 3,4-dicarboxy-2,2,5,5-tetra(2H3)methylpyrrolidin-(3,4-2H2)-(1-15N)-1-oxyl (2H,15N-DCP) and 3,4-dicarboxy-2,2,5,5-tetra(2H3)methylpyrrolidin-(3,4-2H2)-1-oxyl (2H-DCP), were used in the study. A clonogenic cell survival assay was performed with the 2H-DCP radical using squamous cell carcinoma (SCC VII) cells. The time course of EPR signal intensities of intravenously injected 2H,15N-DCP and 2H-DCP radicals were determined in tumor-bearing hind legs of mice (C3H/HeJ, male, n = 5). CW-EPR-based single-point imaging (SPI) was performed for 3D T 2* mapping. RESULTS: 2H-DCP radical did not exhibit cytotoxicity at concentrations below 10 mM. The in vivo half-life of 2H,15N-DCP in tumor tissues was 24.7 ± 2.9 min (mean ± standard deviation [SD], n = 5). The in vivo time course of the EPR signal intensity of the 2H,15N-DCP radical showed a plateau of 10.2 ± 1.2 min (mean ± SD) where the EPR signal intensity remained at more than 90% of the maximum intensity. During the plateau, in vivo 3D T 2* maps with 2H,15N-DCP were obtained from tumor-bearing hind legs, with a total acquisition time of 7.5 min. CONCLUSION: EPR signals of 2H,15N-DCP persisted long enough after bolus intravenous injection to conduct in vivo 3D T 2* mapping with CW-EPR-based SPI.
OBJECTIVES: The aim of this study was to demonstrate the feasibility of in vivo three-dimensional (3D) relaxation time T 2* mapping of a dicarboxy-PROXYL radical using continuous-wave electron paramagnetic resonance (CW-EPR) imaging. MATERIALS AND METHODS: Isotopically substituted dicarboxy-PROXYL radicals, 3,4-dicarboxy-2,2,5,5-tetra(2H3)methylpyrrolidin-(3,4-2H2)-(1-15N)-1-oxyl (2H,15N-DCP) and 3,4-dicarboxy-2,2,5,5-tetra(2H3)methylpyrrolidin-(3,4-2H2)-1-oxyl (2H-DCP), were used in the study. A clonogenic cell survival assay was performed with the 2H-DCP radical using squamous cell carcinoma (SCC VII) cells. The time course of EPR signal intensities of intravenously injected 2H,15N-DCP and 2H-DCP radicals were determined in tumor-bearing hind legs of mice (C3H/HeJ, male, n = 5). CW-EPR-based single-point imaging (SPI) was performed for 3D T 2* mapping. RESULTS:2H-DCP radical did not exhibit cytotoxicity at concentrations below 10 mM. The in vivo half-life of 2H,15N-DCP in tumor tissues was 24.7 ± 2.9 min (mean ± standard deviation [SD], n = 5). The in vivo time course of the EPR signal intensity of the 2H,15N-DCP radical showed a plateau of 10.2 ± 1.2 min (mean ± SD) where the EPR signal intensity remained at more than 90% of the maximum intensity. During the plateau, in vivo 3D T 2* maps with 2H,15N-DCP were obtained from tumor-bearing hind legs, with a total acquisition time of 7.5 min. CONCLUSION: EPR signals of 2H,15N-DCP persisted long enough after bolus intravenous injection to conduct in vivo 3D T 2* mapping with CW-EPR-based SPI.
Entities:
Keywords:
Clonogenic assay; In vivo EPR; In vivo nitroxyl radical kinetics; Nitroxyl radical; Single-point imaging; T 2 * mapping
Authors: Ken-ichiro Matsumoto; Baby Chandrika; Joost A B Lohman; James B Mitchell; Murali C Krishna; Sankaran Subramanian Journal: Magn Reson Med Date: 2003-10 Impact factor: 4.668
Authors: J H Ardenkjaer-Larsen; I Laursen; I Leunbach; G Ehnholm; L G Wistrand; J S Petersson; K Golman Journal: J Magn Reson Date: 1998-07 Impact factor: 2.229
Authors: Oxana Tseytlin; Priyaankadevi Guggilapu; Andrey A Bobko; Hussien AlAhmad; Xuan Xu; Boris Epel; Ryan O'Connell; Emily H Hoblitzell; Timothy D Eubank; Valery V Khramtsov; Benoit Driesschaert; Eiad Kazkaz; Mark Tseytlin Journal: J Magn Reson Date: 2019-06-08 Impact factor: 2.229