The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( ${\mathrm{HO}}_2^{•}$ and ${\mathrm{O}}_2^{•-}$ ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the ${\mathrm{HO}}_2^{•}$ and ${\mathrm{O}}_2^{•-}$ production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of ${\mathrm{HO}}_2^{•}$ and ${\mathrm{O}}_2^{•-}$ in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported. The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( ${\mathrm{HO}}_2^{•}$ and ${\mathrm{O}}_2^{•-}$ ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the ${\mathrm{HO}}_2^{•}$ and ${\mathrm{O}}_2^{•-}$ production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of ${\mathrm{HO}}_2^{•}$ and ${\mathrm{O}}_2^{•-}$ in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported.

Several techniques are under development for image-guidance in particle therapy. Positron (β⁺) emission tomography (PET) is in use since many years, because accelerated ions generate positron-emitting isotopes by nuclear fragmentation in the human body. In heavy ion therapy, a major part of the PET signals is produced by β⁺-emitters generated via projectile fragmentation. A much higher intensity for the PET signal can be obtained using β⁺-radioactive beams directly for treatment. This idea has always been hampered by the low intensity of the secondary beams, produced by fragmentation of the primary, stable beams. With the intensity upgrade of the SIS-18 synchrotron and the isotopic separation with the fragment separator FRS in the FAIR-phase-0 in Darmstadt, it is now possible to reach radioactive ion beams with sufficient intensity to treat a tumor in small animals. This was the motivation of the BARB (Biomedical Applications of Radioactive ion Beams) experiment that is ongoing at GSI in Darmstadt. This paper will present the plans and instruments developed by the BARB collaboration for testing the use of radioactive beams in cancer therapy.

Objective . Beams of stable ions have been a well-established tool for radiotherapy for many decades. In the case of ion beam therapy with stable ¹² C ions, the positron emitters ^10,11 C are produced via projectile and target fragmentation, and their decays enable visualization of the beam via positron emission tomography (PET). However, the PET activity peak matches the Bragg peak only roughly and PET counting statistics is low. These issues can be mitigated by using a short-lived positron emitter as a therapeutic beam. Approach. An experiment studying the precision of the measurement of ranges of positron-emitting carbon isotopes by means of PET has been performed at the FRS fragment-separator facility of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany. The PET scanner used in the experiment is a dual-panel version of a Siemens Biograph mCT PET scanner. Main results. High-quality in-beam PET images and activity distributions have been measured from the in-flight produced positron emitting isotopes ¹¹ C and ¹⁰ C implanted into homogeneous PMMA phantoms. Taking advantage of the high statistics obtained in this experiment, we investigated the time evolution of the uncertainty of the range determined by means of PET during the course of irradiation, and show that the uncertainty improves with the inverse square root of the number of PET counts. The uncertainty is thus fully determined by the PET counting statistics. During the delivery of 1.6 × 10 ⁷ ions in 4 spills for a total duration of 19.2 s, the PET activity range uncertainty for ¹⁰ C, ¹¹ C and ¹² C is 0.04 mm, 0.7 mm and 1.3 mm, respectively. The gain in precision related to the PET counting statistics is thus much larger when going from ¹¹ C to ¹⁰ C than when going from ¹² C to ¹¹ C. The much better precision for ¹⁰ C is due to its much shorter half-life, which, contrary to the case of ¹¹ C, also enables to include the in-spill data in the image formation. Significance . Our results can be used to estimate the contribution from PET counting statistics to the precision of range determination in a particular carbon therapy situation, taking into account the irradiation scenario, the required dose and the PET scanner characteristics.

Charged particle therapy with protons or heavier ions is one of the most effective radiotherapy techniques, but uncertainties in the beam range can limit its efficacy. Radioactive ion beams are ideal for image-guided particle therapy because isotopes that undergo β⁺ decay can be visualized with positron emission tomography. This allows spatial localization of the particle distribution in vivo, which can be correlated with the expected dose deposition for online beam range verification. Here we report the successful treatment of a mouse osteosarcoma using a radioactive ¹¹C-ion beam. The tumour was located in the neck, close to the spinal cord, where deviations of even a few millimetres in the beam range could lead to unintended dose deposition in the spine and radiation-induced myelopathy, an injury to the spinal cord. We achieved complete tumour control with the highest dose of 20 Gy while avoiding paralysis. Low-grade neurological side effects were correlated to the activity measured by positron emission tomography in the spine. The biological washout of the activity from the tumour volume was dependent on the dose, indicating a potential component of vascular damage at high doses. This experiment marks a step towards future clinical applications of radioactive ion beams.

High-Z material nanoparticles are being studied as localized dose enhancers in radiotherapeutic applications. Here, the nano-scale physical dose enhancement of proton, carbon and oxygen ion beam radiation by gold nanoparticles was studied by means of Monte Carlo track structure simulation with the TRAX code. We present 2D distributions and radial profiles of the additional dose and the dose enhancement factor for two geometries which consider an isolated and a water-embedded nanoparticle, respectively. Different nanoparticle sizes (radius of 1.2–22 nm) were found to yield qualitatively different absolute and relative dose enhancement distributions and different maximum dose enhancement factors (up to 20). Whereas the smallest nanoparticles produced the highest local dose enhancement factor close to the metal, larger ones led to lower, more diffuse dose enhancement factors that contributed more at larger distances. Differential absorption effects inside the metal were found to be responsible for those characteristics. For the energy range 15–204 MeVu⁻¹, also a mild trend with ion E/A, regardless of the ion species, was found for embedded nanoparticles. In analogy to the width of the ion track itself, slower ions increased the enhancement at the nanoparticle surface. In contrast, no dependence on linear energy transfer was encountered. For slower ions (3–10 MeVu⁻¹), the enhancement effect began to break down over all distances. Finally, the significance of any indirect physical effect was excluded, giving important hints especially in view of the low probabilities (at realistic concentrations and fluences) of direct ion-NP-hits. The very localized nature of the physical dose enhancement found suggests a strong action upon targets closeby, but no relevant effect at cellular distances. When pondering different possible damage enhancement mechanisms of gold nanoparticles in the context of published in vitro and in vivo experimental results, biological pathways are likely to play the key role.