• Energy Research

Nowadays there is a rising interest towards exploiting new therapeutical beams beyond carbon ions and protons. In particular, [Formula: see text]O ions are being widely discussed due to their increased LET distribution. In this contribution, we report on the first experimental verification of biologically optimized treatment plans, accounting for different biological effects, generated with the TRiP98 planning system with [Formula: see text]O beams, performed at HIT and GSI. This implies the measurements of 3D profiles of absorbed dose as well as several biological measurements. The latter includes the measurements of relative biological effectiveness along the range of linear energy transfer values from ≈20 up to ≈750 keV μ [Formula: see text], oxygen enhancement ratio values and the verification of the kill-painting approach, to overcome hypoxia, with a phantom imitating an unevenly oxygenated target. With the present implementation, our treatment planning system is able to perform a comparative analysis of different ions, according to any given condition of the target. For the particular cases of low target oxygenation, [Formula: see text]O ions demonstrate a higher peak-to-entrance dose ratio for the same cell killing in the target region compared to [Formula: see text]C ions. Based on this phenomenon, we performed a short computational analysis to reveal the potential range of treatment plans, where [Formula: see text]O can benefit over lighter modalities. It emerges that for more hypoxic target regions (partial oxygen pressure of ≈0.15% or lower) and relatively low doses (≈4 Gy or lower) the choice of [Formula: see text]O over [Formula: see text]C or [Formula: see text]He may be justified.

Nowadays there is a rising interest towards exploiting new therapeutical beams beyond carbon ions and protons. In particular, [Formula: see text]O ions are being widely discussed due to their increased LET distribution. In this contribution, we report on the first experimental verification of biologically optimized treatment plans, accounting for different biological effects, generated with the TRiP98 planning system with [Formula: see text]O beams, performed at HIT and GSI. This implies the measurements of 3D profiles of absorbed dose as well as several biological measurements. The latter includes the measurements of relative biological effectiveness along the range of linear energy transfer values from ≈20 up to ≈750 keV μ [Formula: see text], oxygen enhancement ratio values and the verification of the kill-painting approach, to overcome hypoxia, with a phantom imitating an unevenly oxygenated target. With the present implementation, our treatment planning system is able to perform a comparative analysis of different ions, according to any given condition of the target. For the particular cases of low target oxygenation, [Formula: see text]O ions demonstrate a higher peak-to-entrance dose ratio for the same cell killing in the target region compared to [Formula: see text]C ions. Based on this phenomenon, we performed a short computational analysis to reveal the potential range of treatment plans, where [Formula: see text]O can benefit over lighter modalities. It emerges that for more hypoxic target regions (partial oxygen pressure of ≈0.15% or lower) and relatively low doses (≈4 Gy or lower) the choice of [Formula: see text]O over [Formula: see text]C or [Formula: see text]He may be justified.

Purpose: We present an α-irradiation setup for the irradiation of primary human cell cultures under controlled conditions using 241Am α-particles.Materials and Methods: To irradiate samples with α-particles in a valid manner, a reliable dosimetry is a great challenge because of the short α-range and the complex energy spectrum. Therefore, the distance between α-source and sample must be minimal. In the present setup, this is achieved by cells growing on a 2 μm thick biaxially-oriented polyethylene terephthalate (boPET) foil which is only 2.7 mm apart from the source. A precise and reproducible exposure time is realized through a mechanical shutter. The fluence, energy spectra and the corresponding linear energy transfer are determined by the source geometry and the material traversed. They were measured and calculated, yielding a dose rate of 8.2 ± 2.4 Gy/min. To improve cell growth on boPET foils, they were treated with air plasma. This treatment increased the polarity and thus the ability of cells attaching to the surface of the foil. Several tests including cell growth, staining for a marker of DNA double-strand breaks and a colony-forming assay were performed and confirm our dosimetry.Conclusion: With our setup, it is possible to irradiate cell cultures under defined conditions with α-particles. The plasma-treated foil is suitable for primary human cell cultures as shown in cell experiments, confirming also the expected number of particle traversals.

Purpose: We present an α-irradiation setup for the irradiation of primary human cell cultures under controlled conditions using 241Am α-particles.Materials and Methods: To irradiate samples with α-particles in a valid manner, a reliable dosimetry is a great challenge because of the short α-range and the complex energy spectrum. Therefore, the distance between α-source and sample must be minimal. In the present setup, this is achieved by cells growing on a 2 μm thick biaxially-oriented polyethylene terephthalate (boPET) foil which is only 2.7 mm apart from the source. A precise and reproducible exposure time is realized through a mechanical shutter. The fluence, energy spectra and the corresponding linear energy transfer are determined by the source geometry and the material traversed. They were measured and calculated, yielding a dose rate of 8.2 ± 2.4 Gy/min. To improve cell growth on boPET foils, they were treated with air plasma. This treatment increased the polarity and thus the ability of cells attaching to the surface of the foil. Several tests including cell growth, staining for a marker of DNA double-strand breaks and a colony-forming assay were performed and confirm our dosimetry.Conclusion: With our setup, it is possible to irradiate cell cultures under defined conditions with α-particles. The plasma-treated foil is suitable for primary human cell cultures as shown in cell experiments, confirming also the expected number of particle traversals.

To measure the effect of acute oxygen depletion on cell survival for different types of radiation, experiments have been performed using Chinese hamster ovary (CHO) cells and RAT-1 rat prostate cancer cells. A special chamber has been developed to perform irradiations under different levels of oxygenation. The oxygen concentrations used were normoxia (air), hypoxia (94.5% N2, 5% CO2, 0.5% O2) and anoxia (95% N2, 5% CO2). Cells were exposed to X-rays and to C-, N- or O-ions with linear energy transfer (LET) values ranging from 100-160 keV/µm. The oxygen enhancement ratio (OER) and relative biological effectiveness (RBE) values have been calculated from the measured clonogenic survival curves. For both cell lines, the X-ray OER depended on the survival level. For particle irradiation, OER was not dependent on the survival level but decreased with increasing LET. The RBE of CHO cells under oxic conditions reached a plateau for LET values above 100 keV/µm, while it was still increasing under anoxia. In conclusion, the results demonstrated that our chamber could be used to measure radiosensitivity under intermediate hypoxia. Measurements suggest that ions heavier than carbon could be of additional advantage in the irradiation, especially of radioresistant hypoxic tumor regions.

To measure the effect of acute oxygen depletion on cell survival for different types of radiation, experiments have been performed using Chinese hamster ovary (CHO) cells and RAT-1 rat prostate cancer cells. A special chamber has been developed to perform irradiations under different levels of oxygenation. The oxygen concentrations used were normoxia (air), hypoxia (94.5% N2, 5% CO2, 0.5% O2) and anoxia (95% N2, 5% CO2). Cells were exposed to X-rays and to C-, N- or O-ions with linear energy transfer (LET) values ranging from 100-160 keV/µm. The oxygen enhancement ratio (OER) and relative biological effectiveness (RBE) values have been calculated from the measured clonogenic survival curves. For both cell lines, the X-ray OER depended on the survival level. For particle irradiation, OER was not dependent on the survival level but decreased with increasing LET. The RBE of CHO cells under oxic conditions reached a plateau for LET values above 100 keV/µm, while it was still increasing under anoxia. In conclusion, the results demonstrated that our chamber could be used to measure radiosensitivity under intermediate hypoxia. Measurements suggest that ions heavier than carbon could be of additional advantage in the irradiation, especially of radioresistant hypoxic tumor regions.