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

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 x 10(8) to 4.5 x 10(9) 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.

Antiproton radiotherapy.

Antiprotons are interesting as a possible future modality in radiation therapy for the following reasons: When fast antiprotons penetrate matter, protons and antiprotons have near identical stopping powers and exhibit equal radiobiology well before the Bragg-peak. But when the antiprotons come to rest at the Bragg-peak, they annihilate, releasing almost 2 GeV per antiproton-proton annihilation. Most of this energy is carried away by energetic pions, but the Bragg-peak of the antiprotons is still locally augmented with approximately 20-30 MeV per antiproton. Apart from the gain in physical dose, an increased relative biological effect also has been observed, which can be explained by the fact that some of the secondary particles from the antiproton annihilation exhibit high-LET properties. Finally, the weakly interacting energetic pions, which are leaving the target volume, may provide a real time feedback on the exact location of the annihilation peak. We have performed dosimetry experiments and investigated the radiobiological properties using the antiproton beam available at CERN, Geneva. Dosimetry experiments were carried out with ionization chambers, alanine pellets and radiochromic film. Radiobiological experiments were done with V79 WNRE Chinese hamster cells. The radiobiological experiments were repeated with protons and carbon ions at TRIUMF and GSI, respectively, for comparison. Several Monte Carlo particle transport codes were investigated and compared with our experimental data obtained at CERN. The code that matched our data best was used to generate a set of depth dose data at several energies, including secondary particle-energy spectra. This can be used as base data for a treatment planning software such as TRiP. Our findings from the CERN experiments indicate that the biological effect of antiprotons in the plateau region may be reduced by a factor of 4 for the same biological target dose in a spread-out Bragg-peak, when comparing with protons. The extension of TRiP to handle antiproton beams is currently in progress. This will enable us to perform planning studies, where the potential clinical consequences can be examined, and compared to those of other beam modalities such as protons, carbon ions, or IMRT photons.

The biological effectiveness of antiproton irradiation.

BACKGROUND AND PURPOSE: Antiprotons travel through tissue in a manner similar to that for protons until they reach the end of their range where they annihilate and deposit additional energy. This makes them potentially interesting for radiotherapy. The aim of this study was to conduct the first ever measurements of the biological effectiveness of antiprotons. MATERIALS AND METHODS: V79 cells were suspended in a semi-solid matrix and irradiated with 46.7MeV antiprotons, 48MeV protons, or (60)Co gamma-rays. Clonogenic survival was determined as a function of depth along the particle beams. Dose and particle fluence response relationships were constructed from data in the plateau and Bragg peak regions of the beams and used to assess the biological effectiveness. RESULTS: Due to uncertainties in antiproton dosimetry we defined a new term, called the biologically effective dose ratio (BEDR), which compares the response in a minimally spread out Bragg peak (SOBP) to that in the plateau as a function of particle fluence. This value was approximately 3.75 times larger for antiprotons than for protons. This increase arises due to the increased dose deposited in the Bragg peak by annihilation and because this dose has a higher relative biological effectiveness (RBE). CONCLUSION: We have produced the first measurements of the biological consequences of antiproton irradiation. These data substantiate theoretical predictions of the biological effects of antiproton annihilation within the Bragg peak, and suggest antiprotons warrant further investigation.