Radon progeny measurements in a ventilated filter system to study respiratory-supported exposure.

Radon (222Rn) and its progeny are responsible for half of the annual dose from natural radiation and the most frequent cause for lung cancer induction after smoking. During inhalation, progeny nuclides accumulate in the respiratory tract while most of the radon gas is exhaled. The decay of progeny nuclides in the lung together with the high radiosensitivity of this tissue lead to equivalent doses implying a significant cancer risk. Here, we use gamma spectroscopy to measure the attachment of radon progeny on an air-ventilated filter system within a radon enriched atmosphere, mimicking the respiratory tract. A mathematical model was developed to describe the measured time-dependent activities of radon progeny on the filter system. We verified a linear relation between the ambient radon activity concentration during exposure and the amount of decay products on the filter system. The measured activities on the filters and its mathematical description are in good agreement. The developed experimental set-up can thus serve to further investigate the deposition of radon progeny in the respiratory tract under varying conditions for determination of dose conversion factors in radiation protection, which we demonstrate by deriving dose estimations in mouse lung.

Radon Solubility in Different Tissues after Short Term Exposure.

Radon, a naturally occurring radioactive noble gas, contributes significantly to lung cancer when incorporated from our natural environment. However, despite having unknown underlying mechanisms, radon is also used for therapeutic purposes to treat inflammatory diseases such as rheumatoid arthritis. Data on the distribution and accumulation of radon in different tissues represent an important factor in dose determination for risk estimation, the explanation of potential therapeutic effects and the calculation of doses to different tissues using biokinetic dosimetry models. In this paper, radon's solubility in bones, muscle tissue, adipose tissue, bone marrow, blood, a dissolved gelatin and oleic acid were determined. In analogy to current radon use in therapies, samples were exposed to radon gas for 1 h using two exposure protocols combined with established γ-spectroscopic measurements. Solubility data varied over two orders of magnitude, with the lowest values from the dissolved gelatin and muscle tissue; radon's solubility in flat bones, blood and adipose tissue was one order of magnitude higher. The highest values for radon solubility were measured in bone marrow and oleic acid. The data for long bones as well as bone marrow varied significantly. The radon solubility in the blood suggested a radon distribution within the body that occurred via blood flow, reaching organs and tissues that were not in direct contact with radon gas during therapy. Tissues with similar compositions were expected to reveal similar radon solubilities; however, yellow bone marrow and adipose tissue showed differences in solubility even though their chemical composition is nearly the same-indicating that interactions on the microscopic scale between radon and the solvent might be important. We found high solubility in bone marrow-where sensitive hematopoietic cells are located-and in adipose tissue, where the biological impact needs to be further elucidated.

Radon Progeny Adsorption on Facial Masks.

The radioactive noble gas radon and its short-living progeny are inhaled during respiration, depositing their decay energies in the lungs. These progeny are considered responsible for more than 95% of the total effective dose and are, together with radon, classified as carcinogenic for lung cancer. Consequently, filtration of the progeny could reduce the dose to the lungs. In our study, we investigated the filtration properties of FFP2 versus surgical masks (II R) for radon and its decay products. The masks were attached to a measurement device, which enabled determination of the size distribution of radon progeny, ranging from unattached to clustered progeny. In parallel, it measured the radon activity concentration during experiments. By comparing background measurements without mask and experiments with masks, the percentage of retained unattached radon progeny was determined for FFP2 (98.8 ± 0.6%) and II R masks (98.4 ± 0.7%). For clustered progeny, the retained fraction was 85.2 ± 18.1% for FFP2 and 79.5 ± 22.1% for II R masks while radon was not filtered. We can show that masks are effective in filtering radon progeny and thus are capable of reducing the total effective dose to the lungs.

In-vivo dose determination in a human after radon exposure: proof of principle.

Radon-222 is pervasive in our environment and the second leading cause of lung cancer induction after smoking while it is simultaneously used to mediate anti-inflammatory effects. During exposure, radon gas distributes inhomogeneously in the body, making a spatially resolved dose quantification necessary to link physical exposure conditions with accompanying risks and beneficial effects. Current dose predictions rely on biokinetic models based on scarce input data from animal experiments and indirect exhalation measurements of a limited number of humans, which shows the need for further experimental verification. We present direct measurements of radon decay in the abdomen and thorax after inhalation as proof of principle in one patient. At both sites, most of the incorporated radon is removed within ~ 3 h, whereas a smaller fraction is retained longer and accounts for most of the deposited energy. The obtained absorbed dose values were [Formula: see text] µGy (abdomen, radon gas) and [Formula: see text] µGy (thorax, radon and progeny) for a one-hour reference exposure at a radon activity concentration of 55 kBq m-3. The accumulation of long-retained radon in the abdomen leads to higher dose values at that site than in the thorax. Contrasting prior work, our measurements are performed directly at specific body sites, i.e. thorax and abdomen, which allows for direct spatial distinction of radon kinetics in the body. They show more incorporated and retained radon than current approaches predict, suggesting higher doses. Although obtained only from one person, our data may thus represent a challenge for the barely experimentally benchmarked biokinetic dose assessment model.

The history of ion beam therapy in Germany.

The advantageous depth dose profile of ion beams together with state of the art beam delivery and treatment planning systems allow for highly conformal tumor treatments in patients. First treatments date back to 1954 at the Lawrence Berkeley Laboratory (LBL) and in Europe, ion beam therapy started in the mid-1990s at the Paul-Scherrer Institute (PSI) with protons and at the Helmholtz Center for Heavy Ion Research (GSI) with carbon ions, followed by the Heidelberg Ion Therapy Center (HIT) in Heidelberg. This review describes the historical development of ion beam therapy in Germany based on the pioneering work at LBL and in the context of simultaneous developments in other countries as well as recent developments.

Radon Adsorption in Charcoal.

Radon is pervasive in our environment and the second leading cause of lung cancer induction after smoking. Therefore, the measurement of radon activity concentrations in homes is important. The use of charcoal is an easy and cost-efficient method for this purpose, as radon can bind to charcoal via Van der Waals interaction. Admittedly, there are potential influencing factors during exposure that can distort the results and need to be investigated. Consequently, charcoal was exposed in a radon chamber at different parameters. Afterward, the activity of the radon decay products 214Pb and 214Bi was measured and extrapolated to the initial radon activity in the sample. After an exposure of 1 h, around 94% of the maximum value was attained and used as a limit for the subsequent exposure time. Charcoal was exposed at differing humidity ranging from 5 to 94%, but no influence on radon adsorption could be detected. If the samples were not sealed after exposure, radon desorbed with an effective half-life of around 31 h. There is also a strong dependence of radon uptake on the chemical structure of the recipient material, which is interesting for biological materials or diffusion barriers as this determines accumulation and transport.

Radon Exposure-Therapeutic Effect and Cancer Risk.

Largely unnoticed, all life on earth is constantly exposed to low levels of ionizing radiation. Radon, an imperceptible natural occurring radioactive noble gas, contributes as the largest single fraction to radiation exposure from natural sources. For that reason, radon represents a major issue for radiation protection. Nevertheless, radon is also applied for the therapy of inflammatory and degenerative diseases in galleries and spas to many thousand patients a year. In either case, chronic environmental exposure or therapy, the effect of radon on the organism exposed is still under investigation at all levels of interaction. This includes the physical stage of diffusion and energy deposition by radioactive decay of radon and its progeny and the biological stage of initiating and propagating a physiologic response or inducing cancer after chronic exposure. The purpose of this manuscript is to comprehensively review the current knowledge of radon and its progeny on physical background, associated cancer risk and potential therapeutic effects.

α-Irradiation setup for primary human cell cultures.

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.

A combined experimental and theoretical study of radon solubility in fat and water.

Radon is a radioactive noble gas that can enter the human body, thus increasing the risk of lung cancer. But it is also used for treatment of various ailments, most notably rheumatoid arthritis. The accumulation of radon differs between tissues, with particularly high concentrations in fat tissue. To understand the underlying mechanisms, a combination of γ-spectroscopy and molecular dynamics simulations were performed, to study the accumulation of radon gas in contact with several liquids (water, fatty acids). The solubilities, specific for a defined radon activity concentration, are in good agreement and differ by two orders of magnitude between water and fat, caused by radon disrupting the hydrogen bond network of water. In contrast, the energy cost of introducing radon atoms into fat is low due to the dispersive interaction between radon and fat, which is a non-polar solvent. This correlation was also explicitly demonstrated in our simulations by changing the polarization of the solvent.

Modulation power of porous materials and usage as ripple filter in particle therapy.

Porous materials with microscopic structures like foam, sponges, lung tissues and lung substitute materials have particular characteristics, which differ from those of solid materials. Ion beams passing through porous materials show much stronger energy straggling than expected for non-porous solid materials of the same thickness. This effect depends on the microscopic fine structure, the density and the thickness of the porous material. The beam-modulating effect from a porous plate enlarges the Bragg peak, yielding similar benefits in irradiation time reduction as a ripple filter. A porous plate can additionally function as a range shifter, which since a higher energy can be selected for the same penetration depth in the body reduces the scattering at the beam line and therefore improves the lateral fall-off. Bragg curve measurements of ion beams passing through different porous materials have been performed in order to determine the beam modulation effect of each. A mathematical model describing the correlation between the mean material density, the porous pore structure size and the strength of the modulation has been developed and a new material parameter called 'modulation power' is defined as the square of the Gaussian sigma divided by the mean water-equivalent thickness of the porous absorber. Monte Carlo simulations have been performed in order to validate the model and to investigate the Bragg peak enlargement, the scattering effects of porosity and the lateral beam width at the end of the beam range. The porosity is found to only influence the lateral scattering in a negligible way. As an example of a practical application, it is found that a 20 mm and 50 mm plate of Gammex LN300 performs similar to a 3 mm and 6 mm ripple filter, respectively, and at the same time can improve the sharpness of the lateral beam due to its multifunctionality as a ripple filter and a range shifter.

Dosimetric precision of an ion beam tracking system.

BACKGROUND: Scanned ion beam therapy of intra-fractionally moving tumors requires motion mitigation. GSI proposed beam tracking and performed several experimental studies to analyse the dosimetric precision of the system for scanned carbon beams. METHODS: A beam tracking system has been developed and integrated in the scanned carbon ion beam therapy unit at GSI. The system adapts pencil beam positions and beam energy according to target motion. Motion compensation performance of the beam tracking system was assessed by measurements with radiographic films, a range telescope, a 3D array of 24 ionization chambers, and cell samples for biological dosimetry. Measurements were performed for stationary detectors and moving detectors using the beam tracking system. RESULTS: All detector systems showed comparable data for a moving setup when using beam tracking and the corresponding stationary setup. Within the target volume the mean relative differences of ionization chamber measurements were 0.3% (1.5% standard deviation, 3.7% maximum). Film responses demonstrated preserved lateral dose gradients. Measurements with the range telescope showed agreement of Bragg peak depth under motion induced range variations. Cell survival experiments showed a mean relative difference of -5% (-3%) between measurements and calculations within the target volume for beam tracking (stationary) measurements. CONCLUSIONS: The beam tracking system has been successfully integrated. Full functionality has been validated dosimetrically in experiments with several detector types including biological cell systems.

[Heavy ion tumor therapy]. / Tumortherapie mit Schwerionenstrahlen.

Heavy ion tumor therapy can reach a millimeter precision everywhere in the body and a greater biological effectiveness in radioresistant tumors compared to the normal tissue. Therefore it is possible to treat mainly resistant or otherwise inoperable tumors with ion beams with great success. In line with the excellent results achieved in a pilot project at GSI several new centers are under construction. In this article, basics of heavy ion tumor therapy are given and the clinical results of the pilot project are described.

Ion beam radiobiology and cancer: time to update ourselves.

High-energy protons and carbon ions exhibit an inverse dose profile allowing for increased energy deposition with penetration depth. Additionally, heavier ions like carbon beams have the advantage of a markedly increased biological effectiveness characterized by enhanced ionization density in the individual tracks of the heavy particles, where DNA damage becomes clustered and therefore more difficult to repair, but is restricted to the end of their range. These superior biophysical and biological profiles of particle beams over conventional radiotherapy permit more precise dose localization and make them highly attractive for treating anatomically complex and radioresistant malignant tumors but without increasing the severe side effects in the normal tissue. More than half a century since Wilson proposed their use in cancer therapy, the effects of particle beams have been extensively investigated and the biological complexity of particle beam irradiation begins to unfold itself. The goal of this review is to provide an as comprehensive and up-to-date summary as possible of the different radiobiological aspects of particle beams for effective application in cancer treatment.

Comparison of carbon ions versus protons.

At present, beam ion beam therapy has started to spread worldwide. In Europe and Asia, combined carbon/proton facilities are favored, but in the US, only proton centers are under construction. This development is partially due to the different funding procedures and partially due to the more complex physical and especially biologic features of the heavy ions. In this article, the basic properties of both ions are presented, and their features for therapy are outlined. This refers to the dose conformity, the general precision of the treatment, and the ability to monitor via in-beam positron emission tomography the ions range inside the patient. Then the very complex biologic features are treated, and, finally, the treatment plans are compared.

Motion compensation with a scanned ion beam: a technical feasibility study.

BACKGROUND: Intrafractional motion results in local over- and under-dosage in particle therapy with a scanned beam. Scanned beam delivery offers the possibility to compensate target motion by tracking with the treatment beam. METHODS: Lateral motion components were compensated directly with the beam scanning system by adapting nominal beam positions according to the target motion. Longitudinal motion compensation to mitigate motion induced range changes was performed with a dedicated wedge system that adjusts effective particle energies at isocenter. RESULTS: Lateral compensation performance was better than 1% for a homogeneous dose distribution when comparing irradiations of a stationary radiographic film and a moving film using motion compensation. The accuracy of longitudinal range compensation was well below 1 mm. CONCLUSION: Motion compensation with scanned particle beams is technically feasible with high precision.

The absence of an early calcium response to heavy-ion radiation in Mammalian cells.

Intracellular calcium is an important second messenger that regulates many cell functions. Recent studies have shown that calcium ions can also regulate the cellular responses to ionizing radiation. However, previous data are restricted to cells treated with low-LET radiations (X rays, gamma rays and beta particles). In this work, we investigated the calcium levels in cells exposed to heavy-ion radiation of high LET. The experiments were performed at the single ion hit facility of the GSI heavy-ion microprobe. Using a built-in online calcium imaging system, the intracellular calcium concentrations were examined in HeLa cells and human foreskin fibroblast AG1522-D cells before and after irradiation with 4.8 MeV/nucleon carbon or argon ions. Although the experiment was sensitive enough to detect the calcium response to other known stimuli, no response to heavy-ion radiation was found in these two cell types. We also found that heavy-ion radiation has no impact on calcium oscillation induced by hypoxia stress in fibroblast cells.

European developments in radiotherapy with beams of large radiobiological effectiveness.

This paper reviews the European activities in the field of tumour therapy with beams which have a Radio Biological Effectiveness (RBE) larger than 1. Initially neutron beams have been used. Then charged pions promised better cure rates so that their use was pursued in the framework of the ;Piotron' project at the Paul Scherrer Institute (Switzerland). However both approaches did not meet the expectations and in the 80s the EULIMA project became the flagship of these attempts to improve the effects of the delivery of radiation doses of large RBE with respect to photons, electrons and even protons. The EULIMA ion accelerator was never built and it took more than ten years to see the approval, in Heidelberg and Pavia, of the construction of the HIT and CNAO ;dual' centres for carbon ions and protons. In 2008 they will start treating patients. The developments that brought to these construction projects are described together with the special features of these two facilities. The third European dual centre is being built by Siemens Medical Systems in Marburg, Germany, while other facilities have been approved but not yet fully financed in Wiener Neustadt (Austria), Lyon (France) and Uppsala (Sweden). Finally the collaboration activities of the European Network ENLIGHT are presented together with the recent involvements of European industries in the construction of turn-key dual centres and the development of a new accelerator concept for hadrontherapy, the ;cyclinac'.

Simulations to design an online motion compensation system for scanned particle beams.

Respiration-induced target motion is a major problem in intensity-modulated radiation therapy. Beam segments are delivered serially to form the total dose distribution. In the presence of motion, the spatial relation between dose deposition from different segments will be lost. Usually, this results in over- and underdosage. Besides such interplay effects between target motion and dynamic beam delivery as known from photon therapy, changes in internal density have an impact on delivered dose for intensity-modulated charged particle therapy. In this study, we have analysed interplay effects between raster scanned carbon ion beams and target motion. Furthermore, the potential of an online motion strategy was assessed in several simulations. An extended version of the clinical treatment planning software was used to calculate dose distributions to moving targets with and without motion compensation. For motion compensation, each individual ion pencil beam tracked the planned target position in the lateral as well as longitudinal direction. Target translations and rotations, including changes in internal density, were simulated. Target motion simulating breathing resulted in severe degradation of delivered dose distributions. For example, for motion amplitudes of +/-15 mm, only 47% of the target volume received 80% of the planned dose. Unpredictability of resulting dose distributions was demonstrated by varying motion parameters. On the other hand, motion compensation allowed for dose distributions for moving targets comparable to those for static targets. Even limited compensation precision (standard deviation approximately 2 mm), introduced to simulate possible limitations of real-time target tracking, resulted in less than 3% loss in dose homogeneity.