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Feasibility of in vivo three-dimensional T *2 mapping using dicarboxy-PROXYL and CW-EPR-based single-point imaging

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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.

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Number 26249057 (to HH).

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Authors and Affiliations

  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

    Harue Kubota, Denis A. Komarov, Shingo Matsumoto & Hiroshi Hirata

  2. Central Institute of Isotope Science, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-0815, Japan

    Hironobu Yasui

  3. Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido University, North 18, West 9, Kita-ku, Sapporo, 060-0818, Japan

    Osamu Inanami

  4. N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, 9, Ac. Lavrentieva Ave., Novosibirsk, 630090, Russia

    Igor A. Kirilyuk

  5. Department of Biochemistry, West Virginia University, Robert C. Byrd Health Sciences Center, 1 Medical Center Drive, Morgantown, WV, 26506, USA

    Valery V. Khramtsov

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  1. Harue Kubota
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Correspondence to Hiroshi Hirata.

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All animal experiments were in accordance with the Law for The Care and Welfare of Animals in Japan and with protocols approved by the Animal Experiment Committee of Hokkaido University. This article does not contain any studies with human participants performed by any of the authors.

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Kubota, H., Komarov, D.A., Yasui, H. et al. Feasibility of in vivo three-dimensional T *2 mapping using dicarboxy-PROXYL and CW-EPR-based single-point imaging. Magn Reson Mater Phy 30, 291–298 (2017). https://doi.org/10.1007/s10334-016-0606-8

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  • DOI: https://doi.org/10.1007/s10334-016-0606-8

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