V-79 Chinese Hamster cells irradiated with antiprotons, a study of peripheral damage due to medium and long range components of the annihilation radiation

Abstract

Purpose: Radiotherapy of cancer carries a perceived risk of inducing secondary cancer and other damage due to dose delivered to normal tissue. While expectedly small, this risk must be carefully analysed for all modalities. Especially in the use of exotic particles like pions and antiprotons, which annihilate and produce a mixed radiation field when interacting with normal matter nuclei, the biological effective dose far out of field needs to be considered in evaluating this approach. We describe first biological measurements to address the concern that medium and long range annihilation products may produce a significant background dose and reverse any benefits of higher biological dose in the target area.

Materials and methods: Using the Antiproton Decelerator (AD) at CERN (Conseil Européen pour la Recherche Nucléaire) we irradiated V-79 Chinese Hamster cells embedded in gelatine using an antiproton beam with fluence ranging from 4.5 × 10⁸ to 4.5 × 10⁹ particles, and evaluated the biological effect on cells located distal to the Bragg peak using clonogenic survival and the COMET assay.

Results: Both methods show a substantial biological effect on the cells in the entrance channel and the Bragg Peak area, but any damage is reduced to levels well below the effect in the entrance channel 15 mm distal to the Bragg peak for even the highest particle fluence used.

Conclusions: The annihilation radiation generated by antiprotons stopping in biological targets causes an increase of the penumbra of the beam but the effect rapidly decreases with distance from the target volume. No major increase in the biological effect is found in the far field outside of the primary beam.

Keywords:

• antiprotons
• comet assay
• clonogenic assay
• DNA damage

Acknowledgements

The authors express their gratitude to all AD-4/ACE collaborators and in particular to Michael Doser, Dragan Hajdukovic and Gerd Beyer for their active support during the experiments and for assisting in obtaining the necessary funding for this work. The critical reading of the revised manuscript by members of the AD-4 collaboration significantly improved the final product. The experiments would not have been possible without the diligent work by the AD Operating Team to provide the required antiproton beam. The Danish Cancer Society supported this project with a grant.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notes

1 The experiment AD-4/ACE was accepted by the CERN program committee for running parasitically at the Antiproton Decelerator in January 2004. The AD-4 collaboration consists of the following members: Michael H. Holzscheiter¹, Niels Bassler^2,3, Jan Alsner², Gerd Beyer⁴, John J. DeMarco⁵, Michael Doser⁶, Dragan Hajdukovic⁷, Oliver Hartley⁴, Keisuke S. Iwamoto⁵, Oliver Jäkel³, Helge V. Knudsen⁸, Sandra Kovacevic⁷, Søren Pape Møller⁹, Jens Overgaard², Jørgen B. Petersen², Osman Ratib⁴, Timothy D. Solberg¹⁰, Sanja Vranjes¹¹, Bradly G. Wouters¹². 1. University of New Mexico, Albuquerque, NM, USA; 2. Department of Medical Physics and Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; 3. Deutsches Krebsforschungszentrum, Heidelberg, Germany; 4. Hôpital Universitaire de Genève, Geneva, Switzerland; 5. David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; 6. CERN, Geneva, Switzerland; 7. University of Montenegro, Podgorica, Montenegro; 8. Department of Physics & Astronomy, University of Aarhus, Aarhus, Denmark; 9. ISA, University of Aarhus, Aarhus Denmark; 10. University of Nebraska Medical Center, Omaha, NE, USA; 11. VINCA Institute for Nuclear Sciences, Belgrade, Serbia; 12. University of Maastricht, Res. Institute Growth and Development, The Netherlands.

2 Sullivan estimates the local energy deposition of an antiproton near the annihilation point as 30 MeV, which leads to the requirement of 10¹¹ antiprotons for 1 Joule of energy deposition.