Results of heavy ion radiotherapy

The potential of heavy ion therapy for clinical use in cancer therapy stems from the biological parameters of heavy charged particles and their precise dose localization. Biologically, carbon, neon, and other heavy ion beams (up to about silicon) are clinically useful in overcoming the radioresistance of hypoxic tumors, thus increasing the biological effectiveness relative to low linear energy transfer x-ray or electron beams. Cells irradiated by heavy ions show less variation in cell-cycle-related radiosensitivity and decreased repair of radiation injury. The physical parameters of these heavy charged particles allow precise delivery of high doses to tumors while minimizing irradiation of normal tissues. Clinical use requires a close interaction between radiation oncologists, medical physicists, accelerator physicists, engineers, computer scientists, and radiation biologists.     

Method to increase efficiency of irradiation of biological objects by electron beams

The method has been proposed for active control of distribution of the dose caused by an electron beam passed through the medium. The method is based on the influence of magnetic field on charged particles and it allows concentrating of the absorbed dose in the prescribed area. To investigate this method the Monte-Carlo simulations were carried out for 20-70 MeV electrons in 0.5-3 T magnetic field using GEANT program. From the obtained results it follows that in the uniform magnetic field the maximum in distribution of the electron beam dose appears and its shape is similar to Bregg's peak for heavy charged particles. The location of the maximum may be changed by varying beam energy and magnetic fields configuration. For 60-70 MeV beam the maximum may be obtained at the depth of 10-15 cm that is convenient for radiotherapeutic usage.     

Intermediate dosimetric quantities.

The transfer of energy from ionizing radiation to matter involves a series of steps. In wide ranges of their energy spectra photons and neutrons transfer energy to an irradiated medium almost exclusively by the production of charged particles which ionize and thereby produce electrons that can ionize in turn. The examination of these processes leads to a series of intermediate quantities. One of these is kerma, which has long been employed as a measure of the energy imparted in the first of the interactions. It depends only on the fluence of uncharged particles and is therefore--unlike absorbed dose and electron fluence--insensitive to local differences of receptor geometry and composition. An analogous quantity for charged-particle fields, cema (converted energy per unit mass), is defined, which quantifies the energy imparted in terms of the interactions of charged particles, disregarding energy dissipation by secondary electrons. Cema can be expressed as an integral over the fluence of ions times their stopping power. However, complications arise when the charged particles are electrons, and when their fluence cannot be separated from that of the secondaries. The resulting difficulty can be circumvented by the definition of reduced cema. This quantity corresponds largely to the concept employed in the cavity theory of Spencer and Attix. In reduced cema not all secondary electrons but all electrons below a chosen cutoff energy, delta, are considered to be absorbed locally. When the cutoff energy is reduced, cema approaches absorbed dose and thereby becomes sensitive to highly local differences in geometry or composition. With larger values of delta, reduced cema is a useful parameter to specify the dose-generating potential of a charged-particle field 'free in air' or in vacuo. It is nearly equal to the mean absorbed dose in a sphere with radius equal to the range of electrons of energy delta. Reduced cema is a function of the fluence at the specified location at and above the chosen cutoff energy. Its definition requires a modification of restricted linear collision stopping power, L delta, and it is recommended that the definition of L delta be so changed.     

The response of tissue-equivalent proportional counters to heavy ions

The paper presents a theoretical model for the response of a tissue-equivalent proportional counter (TEPC) irradiated with charged particles. Heavy ions and iron ions in particular constitute a significant part of radiation in space. TEPCs are used for all space shuttle and International Space Station (ISS) missions to estimate the dose and radiation quality (in terms of lineal energy) inside spacecraft. The response of the tissue-equivalent proportional counters shows distortions at the wall/cavity interface. In this paper, we present microdosimetric investigation using Monte Carlo track structure calculations to simulate the response of a TEPC to charged particles of various LET (1 MeV protons, 2.4 MeV alpha particles, 46 MeV/nucleon 20Ne, 55 MeV/nucleon 20Ne, 45 MeV/nucleon 40Ar, and 1.05 GeV/nucleon 56Fe). Data are presented for energy lost and energy absorbed in the counter cavity and wall. The model calculations are in good agreement with the results of Rademacher et al. (Radiat. Res. 149, 387-389, 1998), including the study of the interface between the wall and the sensitive region of the counter. It is shown that the anomalous response observed at large event sizes in the experiment is due to an enhanced entry of secondary electrons from the wall into the gas cavity.     

Investigation of the bystander effect in CHO-K1 cells

AimInvestigation of the bystander effect in Chinese Hamster Ovary cells (CHO-K1) co-cultured with cells irradiated in the dose range of 0.1–4 Gy of high LET ¹²C ions and X-rays.BackgroundThe radiobiological effects of charged heavy particles on a cellular or molecular level are of fundamental importance in the field of biomedical applications, especially in hadron therapy and space radiation biology.Materials and methodsA heavy ion ¹²C beam from the Heavy Ion Laboratory of the University of Warsaw (HIL) was used to irradiate CHO-K1 cells. Cells were seeded in Petri dishes specially designed for irradiation purposes. Immediately after irradiation, cells were transferred into transwell culture insert dishes to enable co-culture of irradiated and non-irradiated cells. Cells from the membrane and well shared the medium but could not touch each other. To study bystander effects, a clonogenic survival assay was performed.ResultsThe survival fraction of cells co-cultured with cells irradiated with ¹²C ions and X-rays was not reduced.ConclusionsThe bystander effect was not observed in these studies.     

Cytogenetic effects induced by accelerated carbon ions with shielding

Our work aims to understand the effects of shielding on the induction of biological damage by heavy charged particles and to compare the shielding effects of different materials at the same LET from two aspects: the biological effectiveness including or not including secondary particles emitted at large angles and the biological effectiveness at different angles with respect to the beam direction. We designed and conducted biological experiments to determine the biological effectiveness of 200 MeV/u carbon ions after traversing different shielding materials (Lucite and aluminium). Whole blood samples, which were either attached to the shielding material (48 mm Lucite or 29 mm aluminium)or positioned at 300 cm away from it at different angles with respect to the beam axis, were exposed to carbon ion beams. For comparison, whole blood samples were exposed directly to 200 MeV/u carbon ions. Chromosomal aberrations in lymphocytes were scored. The results indicated that the biological effectiveness per unit dose was not significantly changed by 48 mm Lucite or 29 mm aluminium, and no significant differences were observed in lymphocytes attached to the target and in lymphocytes positioned at a distance of 300 cm away from the target, at 0o angle of the beam axis. However, when plotted as a function of the number of ions hitting the shielding target, the curves are separated and the shield increases the effectiveness per unit ion. The frequency of chromosomal aberrations at tilted angles behind 29 mm Al and 48 mm Lucite was almost the same. These lesions were considered to be caused by secondary particles due to the passage of particles through the shielding materials.     

A new less toxic polymer gel dosimeter: Radiological characteristics and dosimetry properties

PurposeA new polymer gel dosimeter recipe was investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomer 2-Acrylamido 2-Methyl Propane Sulfonic acid (AMPS).MethodsThe new formulation was named PAMPSGAT. The MRI response (R2) of the dosimeters was analyzed for conditions of varying dose, dose rate, and temperature during scanning. Radiological properties of the PAMPSGAT polymer gel dosimeter were investigated.ResultsThe dose-response (R2) of AMPS/Bis appears to be linear over a dose range 10–40 Gy. The percentage of difference between the R2 values for imaging at 15 °C and MRI room temperature is about 4.6% for vial with 40 Gy absorbed dose which decreased to less than 1% for imaging at 20 °C. The percentage difference of Zeff of PAMPSGAT gel and soft tissue was less than 1% in the practical energy range (100 KeV–100 MeV). The electron density of the PAMPSGAT polymer gel was 2.9% higher than that of muscle. Results showed that the sensitivity of PAMPSGAT polymer gel dosimeter irradiated by ⁶⁰Co (energy = 1.25 MeV) is about 27.7% higher than that of irradiated using a 6 MeV Linac system.ConclusionsTemperature during MRI scanning has a small effect on the R2 response of the PAMPSGAT polymer gel dosimeter. Results confirmed tissue equivalency of the PAMPSGAT polymer gel dosimeter in most practical energy range. The PAMPSGAT polymer gel dosimeter response depends on energy and dose rate.     

Analytical theory for the fluence,planar fluence,energy fluence,planar energy fluence and absorbed dose of primary particles and their fragments in broad therapeutic light ion beams

The purpose of the present work is to develop analytical expressions for the depth variation of the fluence, planar fluence, the energy fluence, planar energy fluence, the mean energy and absorbed dose of primary ions and their associated fragments in tissue-like media with ranges of clinical interest. The analytical expressions of the primary ions and associated fragments take into account nuclear interactions, energy losses, range straggling and multiple scattering. The analytical models of the radiation field quantities were compared with the results of the modified Monte Carlo (MC) code SHIELD-HIT₊. The results show that the shape of the depth absorbed dose distribution of the primary particles is characterized by an increasingly steep exponential fluence decrease with depth as the charge and atomic weight increase. This is accompanied by a compensating increased energy loss towards the Bragg peak as the charge of the ion increases. These largely compensating mechanisms are the main reason that the depth absorbed dose curve of all light ions is surprisingly similar. In addition, a rather uniform dose in the plateau region is obtained since the increasing fragment production almost precisely compensates the loss of primaries. The dominating light fragments such as protons and alpha particles are characterized by longer ranges than the primaries and their depth dose curves to some extent coincide well with the depth fluence curves due to a rather slow variation of mean stopping powers. In contrast, the heavier fragments are characterized by the build up of a slowing down spectrum similar to that of the primaries but with initially slightly shorter or longer ranges depending on their mass to atomic number ratio. The presented analytical theory for the light ion penetration in matter agree quite well with the MC and experimental data and may be very useful for fast analytical calculations of quantities like mean energy, fluence, energy fluence, absorbed dose, and LET.     

Neoplastic transformation in vitro by mixed beams of high-energy iron ions and protons

The radiation environment in space is complex in terms of both the variety of charged particles and their dose rates. Simulation of such an environment for experimental studies is technically very difficult. However, with the variety of beams available at the National Space Research Laboratory (NSRL) at Brookhaven National Laboratory (BNL) it is possible to ask questions about potential interactions of these radiations. In this study, the end point examined was transformation in vitro from a preneoplastic to a neoplastic phenotype. The effects of 1?GeV/n iron ions and 1?GeV/n protons alone provided strong evidence for suppression of transformation at doses ≤5?cGy. These ions were also studied in combination in so-called mixed-beam experiments. The specific protocols were a low dose (10?cGy) of protons followed after either 5-15?min (immediate) or 16-24?h (delayed) by 1?Gy of iron ions and a low dose (10?cGy) of iron ions followed after either 5-15?min or 16-24?h by 1?Gy of protons. Within experimental error the results indicated an additive interaction under all conditions with no evidence of an adaptive response, with the one possible exception of 10?cGy iron ions followed immediately by 1?Gy protons. A similar challenge dose protocol was also used in single-beam studies to test for adaptive responses induced by 232?MeV/n protons and (137)Cs γ radiation and, contrary to expectations, none were observed. However, subsequent tests of 10?cGy of (137)Cs γ radiation followed after either 5-15?min or 8?h by 1?Gy of (137)Cs γ radiation did demonstrate an adaptive response at 8?h, pointing out the importance of the interval between adapting and challenge dose. Furthermore, the dose-response data for each ion alone indicate that the initial adapting dose of 10?cGy used in the mixed-beam setting may have been too high to see any potential adaptive response.     

Microbeams of heavy charged particles.

We have established a single cell irradiation system, which allows selected cells to be individually hit with defined number of heavy charged particles, using a collimated heavy-ion microbeam apparatus at JAERI-Takasaki. This system has been developed to study radiobiological processes in hit cells and bystander cells exposed to low dose and low dose-rate high-LET radiations, in ways that cannot be achieved using conventional broad-field exposures. Individual cultured cells grown in special dishes were irradiated in the atmosphere with a single or defined numbers of 18.3 MeV/amu 12C, 13.0 MeV/amu 20Ne, and 11.5 MeV/amu 40Ar ions. Targeting and irradiation of the cells were performed automatically at the on-line microscope of the microbeam apparatus according to the positional data of the target cells obtained at the off-line microscope before irradiation. The actual number of particle tracks that pass through cell nuclei was detected with prompt etching of the bottom of the cell dish made of ion track detector TNF-1 (modified CR-39), with alkaline-ethanol solution at 37 degrees C for 15-30 minutes. Using this system, separately inoculated Chinese hamster ovary cells, confluent normal human fibroblasts, and single plant cells (tobacco protoplasts) have been irradiated. These are the first studies in which single-ion direct hit effect and the bystander effect have been investigated using a high-LET heavy particle microbeam.     

Effects of heavy ion to the primary [correction of rimary] culture of mouse brain cells.

To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05 Gy up to 2.0 Gy. The subsequent biological effects were evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55-200 keV/micrometers) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this report, a result of memory and learning function to adult mice after whole-body and brain local irradiation at carbon ion and iron ion.     

Response of colony-forming units-spleen to heavy charged particles

Survival of colony-forming units-spleen (CFU-S) was measured after single doses of photons or heavy charged particles from the BEVALAC. The purposes were to define the radiosensitivity to heavy ions used medically and to evaluate relationships between relative biological effectiveness (RBE) and dose-averaged linear energy transfer (LET infinity). In in vitro irradiation experiments. CFU-S suspensions were exposed to 220 kVp X rays or to 20Ne (372 MeV/micron) or 40Ar (447 MeV/micron) particles in the plateau portion of the Bragg curve. In in vivo irradiation experiments, donor mice from which CFU-S were harvested were exposed to 12C (400 MeV/micron). 20Ne (400 or 670 MeV/micron), or 40Ar (570 MeV/micron) particles in Bragg peaks spread to 4 or 10 cm by spiral ridge filters. Based on RBE at 10 survival, the maximum RBE of 2.1 was observed for 40Ar particles characterized by an LET infinity of approximately 100 keV/micron. Lower RBEs were determined at lower or higher estimated values of LET infinity and ranged from 1.1 for low energy 40Ar particles to 1.5-1.6 for low energy 12C and 20Ne. The responses of CFU-S are compared with responses of other model systems to heavy charged particles and with the reported sensitivity of CFU-S to neutrons of various energies. The maximum RBE reported here, 2.1 for high energy 40Ar particles, is somewhat lower than values reported for fission-spectrum neutrons, and is appreciably lower than values for monoenergetic 0.43-1.8 MeV neutrons. Low energy 12C and 20Ne particles have RBEs in the range of values reported for 14.7 MeV neutrons.     

Biosorption of heavy metals from aqueous solutions with tobacco dust

A typical lignocellulosic agricultural residue, namely tobacco dust, was investigated for its heavy metal binding efficiency. The tobacco dust exhibited a strong capacity for heavy metals, such as Pb(II), Cu(II), Cd(II), Zn(II) and Ni(II), with respective equilibrium loadings of 39.6, 36.0, 29.6, 25.1 and 24.5 mg of metal per g of sorbent. Moreover, the heavy metals loaded onto the biosorbent could be released easily with a dilute HCl solution. Zeta potential and surface acidity measurements showed that the tobacco dust was negatively charged over a wide pH range (pH > 2), with a strong surface acidity and a high OH⁻ adsorption capacity. Changes in the surface morphology of the tobacco dust as visualized by atomic force microscopy suggested that the sorption of heavy metal ions on the tobacco could be associated with changes in the surface properties of the dust particles. These surface changes appeared to have resulted from a loss of some of the structures on the surface of the particles, owing to leaching in the acid metal ion solution. However, Fourier transform infrared spectroscopy (FTIR) showed no substantial change in the chemical structure of the tobacco dust subjected to biosorption. The heavy metal uptake by the tobacco dust may be interpreted as metal–H ion exchange or metal ion surface complexation adsorption or both.     

Effects of very low fluences of high-energy protons or iron ions on irradiated and bystander cells

In space, astronauts are exposed to radiation fields consisting of energetic protons and high atomic number, high-energy (HZE) particles at very low dose rates or fluences. Under these conditions, it is likely that, in addition to cells in an astronaut's body being traversed by ionizing radiation particles, unirradiated cells can also receive intercellular bystander signals from irradiated cells. Thus this study was designed to determine the dependence of DNA damage induction on dose at very low fluences of charged particles. Novel techniques to quantify particle fluence have been developed at the NASA Space Radiation Biology Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The approach uses a large ionization chamber to visualize the radiation beam coupled with a scintillation counter to measure fluence. This development has allowed us to irradiate cells with 1 GeV/nucleon protons and iron ions at particle fluences as low as 200 particles/cm(2) and quantify biological responses. Our results show an increased fraction of cells with DNA damage in both the irradiated population and bystander cells sharing medium with irradiated cells after low fluences. The fraction of cells with damage, manifest as micronucleus formation and 53BP1 focus induction, is about 2-fold higher than background at doses as low as ～0.47 mGy iron ions (～0.02 iron ions/cell) or ～70 μGy protons (～2 protons/cell). In the irradiated population, irrespective of radiation type, the fraction of damaged cells is constant from the lowest damaging fluence to about 1 cGy, above which the fraction of damaged cells increases with dose. In the bystander population, the level of damage is the same as in the irradiated population up to 1 cGy, but it does not increase above that plateau level with increasing dose. The data suggest that at fluences of high-energy protons or iron ions less than about 5 cGy, the response in irradiated cell populations may be dominated by the bystander response.     

Prevention of Transfusion-Associated Graft-versus-Host Disease by Irradiation: Technical Aspect of a New Ferrous Sulphate Dosimetric System

Irradiation of whole blood and blood components before transfusion is currently the only accepted method to prevent Transfusion-Associated Graft-Versus-Host-Disease (TA-GVHD). However, choosing the appropriate technique to determine the dosimetric parameters associated with blood irradiation remains an issue. We propose a dosimetric system based on the standard Fricke Xylenol Gel (FXG) dosimeter and an appropriate phantom. The modified dosimeter was previously calibrated using a ⁶⁰Co teletherapy unit and its validation was accomplished with a ¹³⁷Cs blood irradiator. An ionization chamber, standard FXG, radiochromic film and thermoluminescent dosimeters (TLDs) were used as reference dosimeters to determine the dose response and dose rate of the ⁶⁰Co unit. The dose distributions in a blood irradiator were determined with the modified FXG, the radiochromic film, and measurements by TLD dosimeters. A linear response for absorbed doses up to 54 Gy was obtained with our system. Additionally, the dose rate uncertainties carried out with gel dosimetry were lower than 5% and differences lower than 4% were noted when the absorbed dose responses were compared with ionization chamber, film and TLDs.     

PADC nuclear track detector for ion spectroscopy in laser-plasma acceleration

The transparent polymer polyallyl-diglycol-carbonate (PADC), also known as CR-39, is widely used as detector for heavy charged particles at low fluence. It allows for detection of single protons and ions via formation of microscopic tracks after etching in NaOH or KOH solutions. PADC combines a high sensitivity and high specificity with inertness towards electromagnetic noise. Present fields of application include laser-ion acceleration, inertial confinement fusion, radiobiological studies with cell cultures, and dosimetry of nuclear fragments in particle therapy. These require precise knowledge of the energy-dependent response of PADC to different ion species. We present calibration data for a new type of detector material, Radosys RS39, to protons (0.2–3 MeV) and carbon ions (0.6–12 MeV). RS39 is less sensitive to protons than other types of PADC. Its response to carbon ions, however, is similar to other materials. Our data indicate that RS39 allows for measuring carbon ion energies up to 10 MeV only from the track diameters. In addition, it can be used for discrimination between protons and carbon ions in a single etching process.     

Ionization and charge-transfer: basic data for track structure calculations

It is widely accepted that an understanding of the detailed structure of charged particle tracks is essential for interpreting the mechanistic consequences of energy deposition by high linear energy transfer (LET) radiation. The spatial relationship of events along the path of a charged particle, including excitation, ionization, and charge-transfer, govern subsequent chemical, biochemical, and biological reactions that can lead to adverse biologic effects. The determination of spatial patterns of ionization and excitation relies on a broad range of cross-section data relating the interactions of charged particles to the molecular constituents of the absorbing medium. It is important that these data be absolute in magnitude, comprehensive in scope, and reliable if accurate assessment of track structure parameters is to be achieved. Great strides have been made in the development of this database, understanding the underlying theory, and developing analytic models, particularly for interactions involving electrons and protons with atoms and molecules. The database is less comprehensive for interactions involving heavier charged particles, especially those that carry bound electrons, and for interactions in condensed phase media. Although there has been considerable progress in understanding the physical mechanisms for interactions involving fast heavy ions and atomic targets during the past few years, we still lack sufficient understanding to confidently predict cross-sections for these ions with biologically relevant material. In addition, little is known of the interaction cross-sections for heavy charged particles as they near the end of their track, i.e., for low velocity ions where collision theory is less well developed and where the particle's net charge fluctuates owing to electron capture and loss processes. This presentation focuses on the current status of ionization and charge-transfer data. Compilations, reviews, Internet sources, theoretical models, and recent data applicable to track structure calculations are discussed.     

Induction of cytogenetic adaptive response in spermatogonia and spermatocytes by pre-exposure of mouse testis to low-dose (12)C(6+) ions

To investigate the effects of pre-exposure of mouse testis to low-dose (12)C(6+) ions on cytogenetics of spermatogonia and spermatocytes induced by subsequent high-dose irradiation, the testes of outbred Kun-Ming strain mice were irradiated with 0.05Gy of (12)C(6+) ions as the pre-exposure dose, and then irradiated with 2Gy as challenging dose at 4h after per-exposure. Poly(ADP-ribose) polymerase (PARPs) activity and PARP-1 protein expression were respectively measured by using the enzymatic and Western blot assays at 4h after irradiation; chromosomal aberrations in spermatogonia and spermatocytes were analyzed by the air-drying method at 8h after irradiation. The results showed that there was a significant increase in the frequency of chromosomal aberrations and significant reductions of PARP activity and PARP-1 expression level in the mouse testes irradiated with 2Gy of (12)C(6+) ions. However, pre-exposure of mouse testes to a low dose of (12)C(6+) ions significantly increased PARPs activity and PARP-1 expression and alleviated the harmful effects induced by a subsequent high-dose irradiation. PARP activity inhibitor 3-aminobenzamide (3-AB) treatment blocked the effects of PARP-1 on cytogenetic adaptive response induced by low-dose (12)C(6+) ion irradiation. The data suggest that pre-exposure of testes to a low dose of heavy ions can induce cytogenetic adaptive response to subsequent high-dose irradiation. The increase of PARP-1 protein induced by the low-dose ionizing irradiation may be involved in the mechanism of these observations.     

High yields of isochromatid breaks and successive formation of chromosome exchanges may lead to reproductive cell death following high-LET irradiation

To clarify the relationship between cell death and chromosomal aberrations following exposure to heavy-charged ion particles beams, exponentially growing Human Salivary Gland Tumor cells (HSG cells) were irradiated with various kinds of high energy heavy ions; 13 keV/μm carbon ions as a low-LET charged particle radiation source, 120 keV/μm carbon ions and 440 keV/μm iron ions as high-LET charged particle radiation sources. X-rays (200 kVp) were used as a reference. Reproductive cell death was evaluated by clonogenic assays, and the chromatid aberrations in G2/M phase and their repairing kinetics were analyzed by the calyculin A induced premature chromosome condensation (PCC) method. High-LET heavy-ion beams introduced much more severe and un-repairable chromatid breaks and isochromatid breaks in HSG cells than low-LET irradiation. In addition, the continuous increase of exchange aberrations after irradiation occurred in the high-LET irradiated cells. The cell death, initial production of isochromatid breaks and subsequent formation of chromosome exchange seemed to be depend similarly on LET with a maximum RBE peak around 100–200 keV/μm of LET value. Conversely, un-rejoined isochromatid breaks or chromatid breaks/gaps seemed to be less effective in reproductive cell death. These results suggest that the continuous yield of chromosome exchange aberrations induced by high-LET ionizing particles is a possible reason for the high RBE for cell death following high-LET irradiation, alongside other chromosomal aberrations additively or synergistically.     

Examination of fragment dose contribution in heavy ion radiotherapy

Heavy-ion radiotherapy is an efficient method for the treatment of deep-seated tumors, because the stopping of ions in a tissue delivers the maximal absorbed dose to the tumor-affected areas with minimal damage to the healthy tissues. However, heavy ions can undergo nuclear reactions, giving products with lower Z-values and hence a longer range in the tissue. This causes a dose increase beyond the mean range of the primary beam. The contribution of such reaction products was examined in an experiment where a stack of tissue-like targets interleaved with CR-39 etched track detectors (ETD) was irradiated with heavy ions. The analysis was performed using a recently developed technique of trajectory tracing, which enables the spectroscopy of fragments with different Z-values.