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PubMed1992

Transient thermal and mechanical response of water subject to ionizing radiation.

The ultrafast transient (10(-14) to 10(-12)S) thermal and mechanical response of water subject to ionizing radiations of different linear energy transfers has been investigated in order to understand the initial events which lead to cell mutation and lethality. Based on computational fluid dynamics, the production of a "thermal spike" around the trajectory of a charged particle and subsequent diffusion of deposited heart are calculated for particles with linear energy transfer (LET) of 4, 40, and 400 keV/microns. A radiation damage region (that is, the so-called "thermal core") is identified, and the transient behavior of the thermal core is studied. The local and transient environment has a dimension of nanometers, a scale which is of critical interest in understanding mechanisms of radiation damage in cells. The radius of the thermal core, Dd, at temperatures (or internal energy density) of up to 1,000 K, is observed to increase with LET, L, as Dd (in nanometers) = C4.L (in keV/microns)0.6, where, for example, C4 = 0.50 for T = 800 degrees C.

Energy Transfer↗

PubMed2000

Estimation of optimum dose per fraction for high LET radiations: implications for proton radiotherapy.

PURPOSE: For high linear energy transfer (LET) radiations, the relative biologic effect (RBE) changes with dose per fraction. Methods for calculating the optimum dose per fraction for high LET radiations should therefore include an allowance for RBE. METHODS AND MATERIALS: The linear-quadratic (LQ) model, and the associated biologic effective dose (BED) concept, has previously been extended to incorporate the RBE effect. Differential calculus is now used to calculate the optimum dose per fraction (z), when high-LET radiation is used, which is given by the solution for z of (g - LATE(alpha/beta)(L)/TUM(alpha/beta)L . RBE(M( z(2))) - 2 . f . g . K . z - (LATE)(alpha/beta)(L) . f . K . RBE(M) = 0 where g is the normal tissue sparing factor, RBE(M) is the maximum RBE value, f the mean interfraction interval, K the daily low-LET BED equivalent dose for clonogen repopulation and (LATE)(alpha/beta)(L) and (TUM)(alpha/beta)(L) are the respective late reacting normal tissue and tumor fractionation sensitivities for low-LET radiation. RESULTS: The optimum dose per fraction for proton therapy is generally lower than that calculated for photons but there is not a simple relationship between the magnitude of the reduction and the assumed value of RBE(M.) Thus(,) generic values of RBE(M) cannot always be used in such calculations. In some cases, where tumor alpha/beta ratios are low (around 5-6 Gy) and where there is good normal tissue sparing, the optimum dose per fraction is relatively large, typically 4-8 Gy. CONCLUSION: BED equations that include the RBE parameter, together with low-LET alpha/beta ratios and repopulation dose equivalents, constitute a rational model of high-LET radiotherapy. In the case of proton beam therapy, a wide range of optimum dose per fraction is predicted.

Dose Fractionation, Radiation↗

PubMed1967

DNA degradation in Escherichia coli 15T-L- induced by fast proton bombardment.

DNA degradation and its temperature dependence as a function of linear energy transfer were studied in Excherichia coli using fast proton irradiation as the initiating agent. The data indicate that radiation-induced DNA degradation can proceed by two processes. The first, or fast component, begins immediately after irradiation with (60)Co gamma-rays or with fast protons at doses less than 10(10) protons/cm(2). The rate is high and involves a maximum of about 50% degradation. It is elicited more efficiently by protons of high linear energy transfer. The second, or slow component, results from higher doses of fast proton bombardment. There is a delay between irradiation and the initiation of this slower component, but 100% of the DNA complement is degraded. The data indicate that both processes are enzyme-mediated, the first probably by normal DNA-related activity and the second by DNAase activity.

Carbon Isotopes↗

PubMed2003

A microdosimetric-kinetic model for the effect of non-Poisson distribution of lethal lesions on the variation of RBE with LET.

The microdosimetric-kinetic (MK) model for cell killing by ionizing radiation is summarized. An equation based on the MK model is presented which gives the dependence of the relative biological effectiveness in the limit of zero dose (RBE1) on the linear energy transfer (LET). The relationship coincides with the linear relationship of RBE1 and LET observed for low LET, which is characteristic of a Poisson distribution of lethal lesions among the irradiated cells. It incorporates the effect of deviation from the Poisson distribution at higher LET. This causes RBE1 to be less than indicated by extrapolation of the linear relationship to higher LET, and to pass through a maximum in the range of LET of 50 to 200 keV per micrometer. The relationship is compared with several experimental studies from the literature. It is shown to approximately fit their results with a reasonable choice for the value of a cross-sectional area related to the morphology and ultrastructure of the cell nucleus. The model and the experiments examined indicate that the more sensitive cells are to radiation at low LET, the lower will be the maximum in RBE they attain as LET increases. An equation that portrays the ratio of the sensitivity of a pair of cell types as a function of LET is presented. Implications for radiotherapy with high-LET radiation are discussed.

Cell Line↗

PubMed1975

The calculation of charged particle fluence and LET spectra for the irradiation of biologically significant materials by neutrons.

As a preliminary step to evaluating recent theories concerning the biological effect of ionizing radiation, the charged particle fluence distributions and the dose distribution in linear energy transfer have been computed analytically for targets of biological and dosimetric interest irradiated by neutrons. Specifically, 14.7 MeV neutrons, the 252Cf neutron spectrum and a cyclotron generated neutron spectrum are considered to irradiate water, tissue-equivalent plastic and standard man tissue and results are given for all these cases. From a knowledge of the target composition, and the cross-sections and kinetics of all the possible neutron induced reactions in the elements hydrogen, carbon, nitrogen and oxygen, the secondary particle spectrum is calculated. By combining with stopping power data for the ions in the target, the charged particle fluence spectra and dose distribution in linear energy transfer are derived. Secondary quantities computed are kerma, energy expended as nuclear elastic scattering, specific ionization and mean quality factor. Stopping powers have been derived from published atomic stopping powers by summing according to the Bragg rule. A comparison between tissue-equivalent plastic and standard man tissue had been made for each of the neutron spectra.

Californium↗

PubMed1998

Dosimetry during the first IBIS facility flight.

The dosimetry of cosmic rays was performed during the first experimental flight of the IBIS facility. Different thermoluminescent detectors (TLD) have been used to measure the contribution of the low linear energy transfer component (LET < 10 keV/micrometer) and plastic nuclear track detectors (PNTD) for the high linear energy tranfer (LET) component. Several parameters of tracks have been measured to determine the LET spectra of primary and secondary charged particles. The total absorbed dose rate (TLD+PNTD) during the flight was 0.23 mGy/day and the dose equivalent rate using the ICRP 60 was 0.52 mSv/day. The corresponding mean quality factor was 2.4. These results are in agreement with those obtained aboard the MIR station with a tissue equivalent proportional counter.

Cosmic Radiation↗

PubMed2006

Glow peak temperature, supralinearity and LET dependence of TLDs--correlation studies.

The study of the well separated low and high temperature glow peaks in CaSO4:Dy and CaF2:Tm was undertaken to develop comparative data on supralinearity of low and high temperature glow peaks for their use in the estimation of elapsed time of exposure and to analyse their responses to low and high-linear energy transfer (LET) radiation. In CaSO4:Dy, unlike its dosimetric peak, the structure of glow peaks at approximately 140 and 400 degrees C remains unchanged (peak position changes within 4 degrees C) with 60Co gamma-ray exposure up to 1 kGy air kerma. The glow peaks at 140 degrees C exhibited higher supralinearity than that of the peaks at 240 and 400 degrees C. In CaF2:Tm, 110 degrees C glow peak exhibited higher supralinearity and higher response to high-LET radiation as compared with 150 degrees C glow peak. No correlation between glow peak temperature and supralinearity or the LET response was observed.

Calcium Fluoride↗

PubMed1993

Study of biological effects of varying mixtures of Cf-252 and gamma radiation on the acute radiation syndromes: relevance to clinical radiotherapy of radioresistant cancer.

PURPOSE: Data for the 30 day bone marrow syndrome (BM-50) and the 6-10 day gastrointestinal (GI-50) syndrome for a one and two fraction schedule and acute and low dose rate irradiation using pure and mixed Cf-252 and photon radiation are presented. METHODS AND MATERIALS: The radiations of Cf-252 is a mixture of neutrons and gamma rays. We total body irradiated Balb/c mice of both sexes with acute Co-60, low dose rate Cs-137 and Cf-252 using a 1 x and 2 x schedule. For low linear energy transfer radiations of Co-60 or Cs-137 there was expected to be an increase in the dose to produce the gastrointestinal and bone marrow syndromes with minimal change for Cf-252 neutrons. However, the radiations from Cf-252 are approximately 65% neutrons and approximately 35% photons and hence some repair may be expected. We further altered the proportion of photons in the Cf-252 radiation field by mixing Cs-137 with the Cf-252 sources and total body irradiated the mice to determine the effects on the syndromes. We determined the effects of mixing Cf-252 neutrons with different proportions of photons on the radiation syndromes. RESULTS: There was increase in BM-50 and GI-50 doses with fractionated or low dose rate photon irradiations and the dose modifying factors were 1.3-1.4 for the GI syndrome and 1.2 for the bone marrow syndrome. For Cf-252 there was minimal fractionation effect for the GI-50 syndrome, which increased by a 1.1 for x 1 vs. x 2 fractions; for the BM-50 syndrome it rose by a 1.1 factor. For LDR Cs-137 the dose for the GI-50 syndrome rose by a 2.2 fold. For mixed neutron-photon radiation of 0%, 15%, 35%, and 65% eta/gamma mixtures, the dose to produce the BM-50 and GI-50 endpoints dropped sharply from 0 to 35% neutrons and remained flat thereafter. CONCLUSION: For major tissues such as the bone marrow and G-I tract, Cf-252 behaved as high linear energy transfer for mixtures of neutrons and gamma rays of approximately 35% neutrons when the radiation were delivered simultaneously at the low dose rates studied. There was little or no additional contribution to the effectiveness of the mixed radiations if neutrons contributed 35% or more of the dose.

Animals↗

PubMed1999

The assessment of RBE effects using the concept of biologically effective dose.

PURPOSE: To modify existing linear-quadratic (LQ) equations in order to take account of relative biological effectiveness (RBE) using the concept of biologically effective dose (BED). METHODS AND MATERIALS: Clinically useful forms of the LQ model have been modified to incorporate RBE effects in such a way as to allow comparison between high- and low-LET (linear energy transfer) radiations in terms of similar biological dose units. The new parameter in the formulation is RBEM, the intrinsic (or maximum) RBE at zero dose. The principal assumption (following Kellerer and Rossi; ref. 1) is that high-LET radiation modifies the alpha-coefficient of damage while leaving the beta-coefficient unaltered. RESULTS: The equations allow a quantitative estimation of how the apparent RBE will change with changes in dose/fraction or dose-rate and of how the magnitude and rate of change is governed by the low-LET alpha/beta ratio of the irradiated tissue. The modifications are applicable to all types of radiotherapy (fractionated, continuous low dose-rate, therapy with decaying sources, etc.). In cases where the normal tissue RBEM is greater than that for the tumor, the revised formulation helps explain why there will be situations where therapeutic index will be adversely affected by use of high-LET radiation. Such clinical advantages as have been observed are more likely to result from favorable geometrical sparing of critical normal tissues and/or the fact that slowly growing tumors may have alpha/beta values more typical of late-responding normal tissues. CONCLUSIONS: The incorporation of RBE into existing LQ methodology allows quantitative assessment of clinical applications of high-LET radiations via an examination of the associated BEDs. On the basis of such assessments high-LET radiations are shown to confer few advantages.

Dose Fractionation, Radiation↗

PubMed2006

LET and dose dependence of TLD-100 glow curve after exposure to intermediate-energy ions.

We present results from measurements performed with low fluences (10(5)-10(6) cm(-2)) of 15, 25 and 40 MeV u(-1) carbon, 25 MeV u(-1) oxygen and 40 MeV u(-1) neon ions incident on TLD-100 chips. Dosemeters were arranged individually or in stacks in front of the beam, allowing the study of various linear energy transfer (LET) values simultaneously. The thermoluminescence (TL) total signal is observed to be a linear function of deposited energy. To assess the contribution to the glow curve from the high-temperature peaks, two methods were studied: ratios of peak heights (peak 7 with respect to peak 5), and ratios of areas of the deconvoluted high-temperature peaks with respect to peak 5. The ratios were evaluated as a function of dose, showing in both methods a dependence on LET and ion identity. Some of the studied ions show these ratios to be independent of dose, up to 500 mGy, while for other ions, departures from linearity up to 4.5% +/- 2.5% per 100 mGy are observed at 500 mGy. These results show that, in general, the incident radiation LET is not a parameter that can be deduced from the glow curve.

Artifacts↗

PubMed1997

A Comparison of Water-Sodium Dodecyl Sulfate Phase Transfer Linear Solvation Energy Relationships and Databases

Four linear solvation energy relationship (LSER) studies of solute partitioning in aqueous sodium dodecyl sulfate micellar solutions are compared. Two of the LSERs are based on compilations of literature data obtained from a variety of measurement techniques and under differing experimental conditions. A third study used micellar electrokinetic capillary chromatography (MEKC) to obtain partition coefficients, whereas our approach is based solely on a head space gas chromatographic (HSGC) method. Despite significant differences in the sizes of the solute sets, the four LSERs yield essentially equivalent chemical conclusions regarding the fundamental interactions controlling the partition process. In comparison to MEKC, HSGC does not require the presence of salt or buffers, although it can be done with such additives, including cosurfactants. Additionally, the HSGC method, unlike the MLC method, does not involve assumptions concerning the behavior of any stationary phase. There are few restrictions on the HSGC method since one can use it to study species which are present in very low concentrations and which do not have chromophores. Finally, based on Kamlet's recommendation that three to four solutes are needed to properly define each LSER coefficient, we suggest a set of about 20 preferred solutes to use for future LSER studies of micellar systems.

Journal Article↗

PubMed2005

Optimization of radiobiological effects in intensity modulated proton therapy.

Today, inverse treatment planning for intensity modulated proton therapy (IMPT) usually employs a constant relative biological effectiveness (RBE). In this paper, the potential clinical relevance of RBE variations for scanning techniques in IMPT is investigated, and a new strategy to include the RBE into the inverse planning process is presented. Three-dimensional RBE distributions are calculated based on a phenomenological model that describes the RBE as a function of dose, linear energy transfer (LET) and tissue type in the framework of the linear-quadratic model. This RBE model is integrated into the optimization loop of inverse planning by using a modified version of the standard quadratic objective function, where the physical dose is replaced by the biological effect. This system for "biological optimization" was implemented into a research version of the inverse planning software KonRad and allows the direct optimization of the product of RBE and physical dose. Several treatment plans for a prostate case are presented, which compare the biological with the conventional physical dose optimization for IMPT scanning techniques, in particular distal edge tracking (DET) and the full three-dimensional (3D) modulation of beam spots. Mainly due to their different LET distributions, the RBE effects for these two techniques are quite different: while the RBE distribution was more or less homogeneous in the planning target volume (PTV) for 3D modulation, considerable RBE variations within the PTV were observed for DET. These unfavorable effects could be compensated for by employing the new biological objective function, which led to a more homogeneous distribution of the product of RBE and physical dose in the PTV. The computation time increased by a factor of 2 compared to the optimization of the physical dose. In conclusion, the proposed method allows the simultaneous multifield optimization of the biological effect in a reasonable time, and is therefore well suited for studying the influence of a variable RBE in IMPT as well as for minimizing potentially adverse effects.

Body Burden↗

PubMed1989

Model analysis of Space Shuttle dosimetry data.

An extensive model analysis of plastic track detector measurements of high-LET particles on the Space Shuttle has been performed. Three shuttle flights: STS-51F (low-altitude, high-inclination), STS-51J (high-altitude, low-inclination), and STS-61C (low-altitude, low-inclination) are considered. The model includes contributions from trapped protons and galactic cosmic radiation, as well as target secondary particles. Target secondaries, expected to be of importance in thickly shielded space environments, are found to be a significant component of the measured LET (linear energy transfer) spectra.

Cosmic Radiation↗

PubMed2005

Tumor induction in mice locally irradiated with carbon ions: a retrospective analysis.

Tumor induction in mice legs that were locally irradiated with carbon ions was compared to tumor induction by gamma rays after single and fractionated irradiation. A total of 250 tumors were induced in 1104 mice that received carbon-ion doses of 5 through 65 Gy. A total of 77 tumors were induced in 371 mice that received gamma-ray doses of 45 through 95 Gy. Of 91 carbon-ion induced tumors examined histologically, 97 percent were malignant, and sarcomas such as malignant fibrous histiocytoma (47%) and fibrosarcoma (32%) were most frequently observed. Malignant fibrous histiocytoma was also the most frequently observed tumor (12 out of 20 tumors; 60%) after gamma-ray irradiation, followed by carcinomas (25%) such as adenocarcinoma and squamous cell carcinoma. Neither dose fractionation nor linear energy transfer affected tumor induction for carbon ions and gamma rays. Dose responses were linear for carbon ions and gamma rays, and showed no saturation up to 65 Gy of carbon ions and 95 Gy of gamma rays. The relative biological effectiveness of carbon ions was 2.2 for tumor induction and 1.9 for early skin reaction. We conclude that risk of secondary tumor induction by carbon-ion radiotherapy would not be seriously higher than anticipated.

Animals↗

PubMed2006

Analyses of the EPR responses of sucrose and L-alpha-alanine radicals induced by C, Ne, and Ar ion irradiations.

Using electron paramagnetic resonance (EPR), we investigated the signal responses of sucrose and L-alpha-alanine radicals produced by heavy-ion irradiation with various linear energy transfers (LETs) and absorbed dose. The spin yields for the two compounds showed a linear relation with the absorbed dose, as well as a logarithmic correlation with the LET. A quantitative EPR analysis showed that sucrose was more sensitive to the particle species than that of alanine. Hence, the present EPR results imply that sucrose can be useful as a radiation indicator. Further analysis was carried out for the radical-production cross section, which showed that stable radicals of the two compounds were produced through collisions of several particles with a single molecule.

Alanine↗

PubMed2006

Ionisation density dependence of the optically stimulated luminescence dose-response of AL2O3:C to low-energy charged particles.

The optically stimulated luminescence (OSL) response of Al2O3:C to high doses of gamma or beta irradiation can be used to predict the response of this material to charged particles as a function of particle fluence, particle energy and/or linear energy transfer (LET). In particular, it is predicted that track interaction effects at high particle fluences should result in linear-sublinear growth of the OSL signal. Similar considerations also predict a dependence of the fluence at which sublinearity starts upon the energy of the particles. In this work the OSL response of Al2O3:C to low-energy charged particles was investigated using protons (1, 2 and 4 MeV), carbon ions (13 MeV) and oxygen ions (10 MeV). The sublinear growth predicted above was qualitatively confirmed, but the energy dependence prediction was not. Furthermore, the efficiency of OSL production in the material after charged particle irradiation, compared to that obtained for gamma irradiation, is determined from the dose-response curves by fitting to a simple saturating exponential function. The efficiency values so obtained using this method are compared with those obtained from a conventional single-point measurement in the linear portion of the curve and found to be in good agreement. In general, the efficiency decreases as the LET of the particle increases. The present data are compared with published data obtained using high-energy charged particles and the results show that the efficiency is not a unique function of LET.

Aluminum Oxide↗

PubMed2004

Monte-Carlo calculations of radial dose and restricted-let for protons in water.

A new Monte-Carlo code for event-by-event simulation of the transport of energetic non-relativistic protons (approximately 0.5-10 MeV) and all their secondary electrons (down to 1 Ry) in both the vapour and liquid phases of water is presented. A unified particle-water inelastic model for both phases of water has been developed based on experimental optical data and elements of the Bethe theory. The model applies to both electrons and heavy-charged particles and is particularly suitable for extension to other media of biological relevance (organic polymers, DNA, etc.). Condensed-phase effects are included in the liquid version (MC4L) by means of the dielectric functions which, essentially, substitute the oscillator-strength used in the vapour version (MC4V). The results in the form of radial dose distributions and spatially restricted linear energy transfer are presented and compared with the literature.

Algorithms↗

PubMed1995

Induction of HPRT- mutants in Chinese hamster V79 cells after heavy ion exposure.

The induction of resistance to 6-thioguanine by heavy ion exposure was investigated with various accelerated ions (oxygen-uranium) up to linear energy transfer (LET) values of about 15,000 keV/microns. Survival curves are exponential with fluence; mutation induction shows a linear dependence. Cross-sections (sigma i: inactivation, sigma m: mutation) were derived from the respective slopes. Generally, sigma i rises over the whole LET range, but separates into different declining curves for single ions with LET values above 200 keV/microns. Similar behaviour is seen for sigma m. The new SIS facility at GSI, Darmstadt, makes it possible to study the effects of ions with the same LET but very different energies and track structures. Experiments using nickel and oxygen ions (up to 400 MeV/u) showed that inactivation cross-sections do not depend very much on track structure, i.e. similar values are found with different ions at the same LET. This is not the case for mutation induction, where very energetic ions display considerably smaller induction cross-sections, compared with low-energy ions of identical LET. Preliminary analyses using the polymerase chain reaction (PCR) demonstrate that even heavy ions cause "small alterations" (small deletions or base changes). The proportion of the total deletions seems to increase with LET.

Animals↗