The Biological Effectiveness of Antiprotons
Prof. Michael Holzscheiter (Sante Fe, USA / Cern)

The AD-4/ACE collaboration was formed in 2003 to experimentally study the possibility of using antiprotons in radiotherapy applications. This idea was originally proposed in the 1980’s by Gray and Kalogeropoulos, and the enhanced energy deposition of antiprotons at the end of range compared to protons was measured at LEAR by Tony Sullivan in 1985. An increase in physical dose deposition of a factor of two compared to protons for identical dose deposition in the entrance channel was found. While this is a small amount of energy in comparison to the 1.9 GeV annihilation energy, it is a clinically significant increase in the therapeutic ratio potentially achievable. We expect this physical advantage of antiprotons to be augmented by the fact that the additional energy deposited locally in the vicinity of the annihilation vertex contains components with high linear energy transfer (LET), and therefore an expected higher relative biological efficiency (RBE).
Initial test experiments using a beam of 47 MeV antiprotons extracted from the AD into a biological target consisting of V79-WNRE cells embedded in gelatin reported an overall increase of the biological effective dose between entrance channel and Bragg peak (BEDR) of about 4. Based on these early findings the experiment was upgraded to use a 126 MeV energy beam, providing a penetration depth in water of about 11 cm, allowing a clear separation of entrance channel and Bragg peak region as well as the build-up of a clinical spread-out Bragg peak (SOBP). Absolute dosimetry along the beam path in the target enables us to extract the relative biological efficiency (RBE) compared to low LET x-ray radiation, and compare these results to measurements performed with other modalities. We observe not only an increase in RBE in the Bragg peak compared to the entrance channel, we also see a distinct difference in the transition between low RBE and high RBE regions in antiproton and carbon ions.
These data, while still being augmented with new measurements for biological reproducibility, can now be used to perform comparative dose planning exercises using Monte Carlo codes and to search for specific cancer incidences where the unique properties of antiprotons could provide a true benefit to the patient. This presentation will describe the fundamental ideas of the use of antiprotons in radiotherapy, the experimental set-up, the different measurements performed, and will summarize the relevant findings to date.