Advertisement

Cell Biochemistry and Biophysics

, Volume 75, Issue 3–4, pp 295–298 | Cite as

Spin Lattice Relaxation EPR pO2 Images May Direct the Location of Radiation Tumor Boosts to Enhance Tumor Cure

  • Boris Epel
  • Martyna Krzykawska-Serda
  • Victor Tormyshev
  • Matthew C. Maggio
  • Eugene D. Barth
  • Charles A. Pelizzari
  • Howard J. HalpernEmail author
Original Paper

Abstract

Radiation treatment success and high tumor oxygenation and success have been known to be highly correlated. This suggests that radiation therapy guided by images of tumor regions with low oxygenation, oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. Before applying the technique to human subjects, OGRT needs to be tested in animals, most easily in rodents. Electron paramagnetic resonance imaging provides quantitative maps of tissue and tumor oxygen in rodents with 1 mm spatial resolution and 1 torr pO2 resolution at low oxygen levels. The difficulty of using mouse models is their small size and that of their tumors. To overcome this we used XRAD225Cx micro-CT/ therapy system and 3D printed conformal blocks. Radiation is delivered first to a uniform 15% tumor control dose for the whole tumor and then a boost dose to either hypoxic tumor regions or equal volumes of well oxygenated tumor. Delivery of the booster dose used a multiple beam angles to deliver radiation beams whose shape conforms to that of all hypoxic regions or fully avoids those regions. To treat/avoid all hypoxic regions we used individual radiation blocks 3D-printed from acrylonitrile butadiene styrene polymer infused with tungsten particles fabricated immediately after imaging to determine regions with pO2 less than 10 torr. Preliminary results demonstrate the efficacy of the radiation treatment with hypoxic boosts with syngeneic FSa fibrosarcoma tumors in the legs of C3H mice.

Keywords

Electron paramagnetic resonance imaging Radiation treatment Oxygen imaging Image-guided radiation therapy Spin lattice relaxation imaging 

Notes

Acknowledgements

Grant Support: US NIH P41EB002034; R01CA098575; R50 CA211408.

Compliance with Ethical Standards

Conflict of Interest

US patent 8,664,955 was recently awarded to HH and BE. They are members of a start-up company O2M to market the pO2 imaging technology.

References

  1. 1.
    Leibel, S. A., Fuks, Z., Zelefsky, M. J., Hunt, M., Burman, C. M., Mageras, G. S., Chui, C. S., Jackson, A., Amols, H. I., & Ling, C. C. (2003). Technological advances in external-beam radiation therapy for the treatment of localized prostate cancer. Seminars in Oncology, 30, 596–615.CrossRefPubMedGoogle Scholar
  2. 2.
    Mundt, A., & Roeske, J. (2005). Intensity Modulated Radiation Therapy. Hamilton, Ontario: B.C.Decker.Google Scholar
  3. 3.
    Vaupel, P., & Mayer, A. (2007). Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metast Rev, 26, 225–239.  https://doi.org/ 10.1007/s10555-007-9055-1.CrossRefGoogle Scholar
  4. 4.
    Graeber, T. G., Osmanian, C., Jacks, T., Housman, D. E., Koch, C. J., Lowe, S. W., & Giaccia, A. J. (1996). Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature, 379, 88–91.CrossRefPubMedGoogle Scholar
  5. 5.
    Elas, M., Bell, R., Hleihel, D., Barth, E. D., Mcfaul, C., Haney, C. R., Bielanska, J., Pustelny, K., Ahn, K. H., Pelizzari, C. A., Kocherginsky, M., & Halpern, H. J. (2008). Electron paramagnetic resonance oxygen image hypoxic fraction plus radiation dose strongly correlates with tumor cure in FSA fibrosarcomas. International Journal of Radiation Oncology, Biology, Physics, 71, 542–549.  https://doi.org/ 10.1016/j.ijrobp.2008.02.022.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Elas, M., Magwood, J. M., Butler, B., Li, C., Wardak, R., Barth, E. D., Epel, B., Rubinstein, S., Pelizzari, C. A., Weichselbaum, R. R., & Halpern, H. J. (2013). EPR oxygen images predict tumor control by a 50% tumor control radiation dose. Cancer Research, 73, 5328–5335.  https://doi.org/ 10.1158/0008-5472.Can-13-0069.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Epel, B., Sundramoorthy, S. V., Mailer, C., & Halpern, H. J. (2008). A versatile high speed 250-MHz pulse imager for biomedical applications. Concepts in Magnetic Resonance. Part B, Magnetic Resonance Engineering, 33B, 163–176.  https://doi.org/ 10.1002/Cmr.B.20119.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Trukhin, D. V., Rogozhnikova, O. Y., Troitskaya, T. I., Vasiliev, V. G., Bowman, M. K., & Tormyshev, V. M. (2016). Facile and high-yielding synthesis of TAM biradicals and monofunctional TAM radicals. Synlett : Accounts and Rapid Communications in Synthetic Organic Chemistry, 27, 893–899.  https://doi.org/ 10.1055/s-0035-1561299.PubMedGoogle Scholar
  9. 9.
    Epel, B., Bowman, M. K., Mailer, C., & Halpern, H. J. (2014). Absolute oxygen R1e imaging in vivo with pulse electron paramagnetic resonance. Magnetic Resonance in Medicine, 72, 362–368.  https://doi.org/ 10.1002/mrm.24926.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Boris Epel
    • 1
    • 2
  • Martyna Krzykawska-Serda
    • 1
    • 2
  • Victor Tormyshev
    • 2
    • 3
  • Matthew C. Maggio
    • 1
    • 2
  • Eugene D. Barth
    • 1
    • 2
  • Charles A. Pelizzari
    • 1
    • 2
  • Howard J. Halpern
    • 1
    • 2
    Email author
  1. 1.Department of Radiation and Cellular OncologyUniversity of ChicagoChicagoUSA
  2. 2.Center for Electron Paramagnetic Resonance Imaging for In Vivo PhysiologyUniversity of ChicagoChicagoUSA
  3. 3.Novosibirsk Institute of Organic Chemistry, (NIOC)NovosibirskRussia

Personalised recommendations