Alanine response to low energy synchrotron x-ray radiation.

Objective. The radiation response of alanine is very well characterized in the MV photon energy range where it can be used to determine the dose delivered with an accuracy better than 1%, making it suitable as a secondary standard detector in cancer radiation therapy. This is not the case in the very low energy keV x-ray range where the alanine response is affected by large uncertainties and is strongly dependent on the x-ray beam energy. This motivated the study undertaken here.Approach. Alanine pellets with a nominal thickness of 0.5 mm and diameter of 5 mm were irradiated with monoenergetic x-rays at the Diamond Light Source synchrotron, to quantify their response in the 8-20 keV range relative to60Co radiation. The absorbed dose to graphite was measured with a small portable graphite calorimeter, and the DOSRZnrc code in the EGSnrc Monte Carlo package was used to calculate conversion factors between the measured dose to graphite and the absorbed dose to water delivered to the alanine pellets. GafChromic EBT3 films were used to measure the beam profile for modelling in the MC simulations.Main results. The relative responses measured in this energy range were found to range from 0.616 to 0.643, with a combined relative expanded uncertainty of 3.4%-3.5% (k= 2), where the majority of the uncertainty originated from the uncertainty in the alanine readout, due to the small size of the pellets used.Significance. The measured values were in good agreement with previously published data in the overlapping region of x-ray energies, while this work extended the dataset to lower energies. By measuring the response to monoenergetic x-rays, the response to a more complex broad-spectrum x-ray source can be inferred if the spectrum is known, meaning that this work supports the establishment of alanine as a secondary standard dosimeter for low-energy x-ray sources.

ENDOR study on the dynamic properties of the first stable paramagnetic center in gamma-irradiated L-alanine crystals.

Dynamic properties of the first stable l-alanine radical, SAR1, induced by gamma-irradiation of l-alanine crystals, have been investigated by the electron nuclear double resonance technique (ENDOR). The study focuses on the dynamic properties of the alpha-proton hyperfine splitting in the temperature range from 180 to 320 K. In this region the motion of the NH(3)(+) and CH(3) groups exhibits slow and fast motional dynamics in comparison to the nuclear and electron Larmor frequencies, respectively. Evidence for different conformations of the SAR1 center is presented on the basis of thermodynamic properties of the alpha-hyperfine splitting. The activation processes causing the broadening of the ENDOR lines are studied. At room temperature the motional dynamics of the SAR1 center are modulated by the dynamics of the charged, neighboring NH(3)(+) group.

The Effect of gadolinium on the ESR response of alanine and ammonium tartrate exposed to thermal neutrons.

Many efforts have been made to develop neutron capture therapy (NCT) for cancer treatment. Among the challenges in using NCT is the characterization of the features of the mixed radiation field and of its components. In this study, we examined the enhancement of the ESR response of pellets of alanine and ammonium tartrate with gadolinium oxide exposed to a thermal neutron beam. In particular, the ESR response of these dosimeters as a function of the gadolinium content inside the dosimeter was analyzed. We found that the addition of gadolinium improves the sensitivity of both alanine and ammonium tartrate. However, the use of gadolinium reduces or abolishes tissue equivalence because of its high atomic number (Z(Gd) = 64). Therefore, it is necessary to find the optimum compromise between the sensitivity to thermal neutrons and the reduction of tissue equivalence. Our analysis showed that a low concentration of gadolinium oxide (of the order of 5% of the total mass of the dosimeter) can enhance the thermal neutron sensitivity more than 13 times with an insignificant reduction of tissue equivalence.

Response of the alanine/ESR dosimetry system to MV X-rays relative to (60)Co radiation.

The measurand relevant in dosimetry for radiation therapy is the absorbed dose to water, D(W). The Physikalisch-Technische Bundesanstalt (PTB) has established a secondary standard for D(W) for high-energy photon and electron radiation based on electron spin resonance (ESR) of the amino acid alanine. Since the calibration is usually performed using (60)Co radiation while a huge part of the external radiation therapy is done with high-energy x-rays from linear accelerators, determination of the response is an important issue. The results presented in this paper are the most accurate ones available today with uncertainties assigned to the relative response for 8 MV and 16 MV of the order of 0.3%. The experimental results are compared to Monte Carlo simulations using the EGSnrc software package. In the appendix, it is demonstrated how mean values from repetitive irradiations and their uncertainties are obtained in a consistent way using Bayesian statistics, even in the presence of at first sight inconsistent data. It is important to note that the formulae derived to obtain the final results follow from first principles, without recurring to ad hoc solutions or simple recipes and are valid for all kinds of repetitive measurements.

EPR spectra of gamma-irradiated DL-alpha-alanine supported on molecular sieves.

The aim of the work was to collect information concerning boundary effects which are suspected in alpha-alanine dosimeters consisted of powdered microcrystalline alpha-alanine and binders. In our experiments the conventional binders were replaced by molecular sieves (MS). MS are inorganic porous materials (host structures) with well organized and uniform intra-crystalline pore systems of nano-scale size. The guest molecules can be either physically adsorbed on very large inner MS surface, or chemically bound to the active sites. They can be also encapsulated inside the intracrystalline cavities. The EPR spectra of gamma irradiated DL-alpha-alanine supported on NaY, CeY, SOD, mordenite, ZSM-5 and ALPO(4)-5 were very similar to that one observed for irradiated microcrystalline DL-alpha-alanine. In the case of alanine supported on HY an initial EPR spectrum was different and only after some weeks it made resemble to the well known quintet observed in microcrystalline samples. In sodalites synthesized in the presence of DL-alpha-alanine EPR signal appeared in non-irradiated sample was very low and structureless. The irradiated sample showed a distinct spectrum which was quite different from that one observed for crystalline DL-alpha-alanine.

Sucrose radical-production cross-section regarding heavy-ion irradiation.

We investigated the sucrose radical-production cross-section induced by heavy-ion irradiation. L-alanine was also used in order to compare radical yield and cross-section. The stable free radicals after irradiation were analyzed by electron paramagnetic resonance (EPR). The radical yield obtained by the irradiated samples had a logarithmic correlation with the LET (linear energy transfer). Quantitative EPR analyses showed that radical productions for sucrose and L-alanine vary both by different particle irradiation and the LET under the same absorbed dose. Furthermore, the cross-sections of radical productions for samples were calculated. Both cross-sections for C ions irradiation under LET 30 keV/microm at 50 Gy dose were approximately 3.0x10(-9) microm(2), taking account of the molecular areas of the samples. The values of the cross-sections imply that multiple ionizing particles involve producing stable radicals.

The effect of dose on light-sensitivity of radicals in alanine EPR dosimeters.

In this work we present a study of light-induced effects on free radicals and their transformations in gamma-irradiated pure L-alanine and in commercially available alanine detectors: rods, pellets and films. Samples irradiated to doses from 2 Gy to 4000 kGy were exposed to light from a fluorescent lamp and to ordinary daylight. The observed changes in EPR spectra of the samples were analyzed with regard to their intensity and shape. The shape analysis was based on numerical decomposition of the measured spectra into model spectra reflecting contributions of R1, R2 and R3 radical populations in the samples. The illumination of alanine dosimeters resulted in significant decrease of the central EPR line and was accompanied by distinct variations in the shape of EPR spectra. The rate of light-induced decay in spectra amplitude was found to be dependent on dose of ionizing radiation--the sensitivity to light was decreasing with increase in dose in all detectors in the 2-5x10(5) Gy dose range. The exposure of gamma-irradiated (to 300 Gy) alanine to normal, diffused daylight resulted in decay of the signal amplitude at rate about 0.5% per week. It was shown that decay in the R1 component was responsible for the observed reduction of the spectra amplitude. The observed increase in R2 contributions in samples exposed to light confirmed a hypothesis of R-->R2 radical transformations promoted by visible light. The reported effects indicate a necessity of protection of irradiated dosimeters from their prolonged exposure to light.

ESR response to gamma-rays of alanine pellets containing B(OH)3 or Gd2O3.

ESR response to gamma-irradiation (1-50 Gy) of blends containing alanine and either B(OH)(3) or Gd(2)O(3) is reported. The sensitivity of the alanine--B(OH)(3) blend is comparable to the sensitivity of pure alanine, although its lowest detectable dose, LDD, is smaller ( approximately 1.3 Gy) than that of pure alanine ( approximately 2.9 Gy). Alanine with Gd(2)O(3) is about two times more sensitive than pure alanine, and its LDD is 0.8 Gy. The better sensitivity and LDD are probably due to the high atomic number (Z=64) of gadolinium, which enhances the interaction probability with photons and, consequently, the radical yield. This study suggests that other high-Z atoms may be useful for increasing the sensitivity of the response of alanine to gamma-radiation.

Alanine blends for ESR measurements of thermal neutron fluence in a mixed radiation field.

In this paper, the results of a study on the electron spin resonance (ESR) dosimetry to measure thermal neutron fluence in a mixed radiation field (neutron and photons) are presented. The ESR responses of alanine dosemeters with different additives are compared. In particular, the (10)B-acid boric and the Gd-oxide were chosen to enhance the sensitivity of alanine dosemeters to thermal neutrons. Irradiations were carried out inside the thermal column of the TAPIRO reactor of the ENEA center, Casaccia Rome. The main results are a greater neutron sensitivity and a smaller lowest detectable fluence for the dosemeters with gadolinium than for dosemeters of alanine with (10)B, which is well known to be much more sensitive to thermal neutrons than simple alanine.

Response of alanine and radio-photo-luminescence dosemeters to mixed high-energy radiation fields.

Alanine and Radio-Photo-Luminescence (RPL) dosemeters are passive dosemeters used to monitor absorbed dose in all kind of radiation fields. However, up to now both dosemeter types are calibrated to photon sources only. In order to study the response of RPL and alanine dosemeters to mixed high-energy particle fields like those occurring at CERN's accelerators, an irradiation campaign at the CERN-EC High-Energy Reference field Facility (CERF-field) was performed. In this facility a copper target is irradiated by hadrons with a momentum of 120 GeV/c. Dosemeters were exposed to various mixed radiation fields by placing them at various positions on the surface of the target. In addition to the experiment FLUKA Monte Carlo simulations were carried out, which provide information concerning the energy deposition at the dosemeter locations. This paper compares the measurements with the simulation results and discusses the radiation field compositions present at the various dosemeter positions on the target.

Evidence for disorder in L-alanine lattice detected by Pulsed-EPR spectroscopy at cryogenic temperatures.

The unusual behavior of lattice dynamics of L-alanine has been assigned to intermolecular dynamics and localization of vibrational energy. Recent heat capacity and Pulsed-EPR measurements support presence of thermally activated dynamic orientational disorder in the L-alanine lattice below 20 K. In the present study, the additional evidence for possible thermally activated disordered behavior of L-alanine lattice have been obtained by investigating dependences of longitudinal relaxation time of first stable L-alanine radical, SAR1, on sample cooling rates for the same low temperature interval. The obtained relaxation time by Pulsed-EPR shows clear dependence on cooling rates and this behavior can be explained within two types of suggested spin-lattice relaxation mechanisms for the paramagnetic centers in the hydrogen-bonded organic crystal.

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.

Solid state "self-calibrated" EPR-dosimeters-advantageous and shortcomings.

EPR dosimetry method with alpha-alanine as radiation sensitive material (RSM) is widely used in high dose dosimetry laboratories. However, it is not suitable for routine industrial applications mainly because of difficult EPR measurement procedure. In order to simplify quantitative EPR dosimetry measurements Yordanov and Gancheva developed so-called "self-calibrated" (sc) dosimeters consists of RSM (alpha-alanine, sugar, other ones), Mn2+/MgO as internal EPR intensity standard (IES) and a binder. The aim of this work was to check dosimetric properties of two experimental batches of sc EPR dosimeters with alpha-alanine and sugar as RSM, Mn2+/MgO as IES and paraffin as a binder. The percentage content of the components was 60, 5 and 35% (w/w), respectively. It was established that the investigated alanine sc-dosimeters are about two times more sensitive than the sugar ones. The dose-response coefficient, K(dr) of sc-alanine dosimeters was stable in all investigated dose range from 1 to 23 kGy. The K(dr)-value of sugar sc-dosimeters decreased with the dose what was in a contradiction to the results pointed to the high stability of radiation generated sugar radicals. The observed effect arose probably from the special chemical procedure used for the sc-sugar dosimeters production. The results confirmed an expectation that the position of sc dosimeter in the cavity is not important factor for accurate dose evaluation. It allows to read-out dosimetric signals in shorter time, with lower uncertainty and on less sophisticate EPR-spectrometers than that commonly used till now. The main shortcomings of sc dosimeters are: (a) the limitation of RSM suitable for sc dosimeters to these ones having strictly linear signal to dose characteristic; (b) necessity to assure very good homogeneity of dosimeter material; and (c) the cost of IES present in the amount of some percent in each sc dosimeter.

Use of commercial alanine and TL dosemeters for dosimetry intercomparisons among Italian radiotherapy centres.

In the implementation of a large-scale dosimetry intercomparison one of the main constraints is the availability of large number of dosemeters of the highest quality. Therefore, ISS tested the possibility of using commercially available dosemeters, alanine pellets and thermoluminescence (TL) dosimetry chips, for transfer dosimetry within the Italian intercomparison programme. In this work the characterisation of commercial alanine and TL dosemeters along with the ISS dose assessment procedure used in the Italian intercomparison are reported. Results demonstrate the feasibility of the ISS approach to transfer dosimetry since it is possible to measure 10 Gy with a combined uncertainty of 1% (1sigma) and 1 Gy with a combined uncertainty of 1.7% (1sigma) with alanine and TL dosemeters, respectively.

A study of the irradiation temperature coefficient for L-alanine and DL-alanine dosemeters.

Alanine dosimetry is now well established both as a reference and routine dosemeter for industrial irradiation processing. Accurate dosimetry under the relatively harsh conditions of industrial processing requires a characterisation of the parameters that influence the dosemeter response. The temperature of the dosemeter during irradiation is a difficult quantity to measure so that the accuracy of the temperature coefficient that governs the dosemeter response becomes a critical factor. Numerous publications have reported temperature coefficients for several types of alanine dosemeters. The observed differences in the measured values were commonly attributed to the differences in the polymer binder or the experimental design of the measurement. However, the data demonstrated a consistent difference in the temperature coefficients between l-alanine and dl-alanine. Since there were no commonalities in the dosemeter composition or the measurement methods applied, a clear conclusion is not possible. To resolve this issue, the two isomeric forms of alanine dosemeters were prepared and irradiated in an identical manner. The results indicated that the dl-alanine temperature coefficient is more than 50% higher than the l-alanine temperature coefficient.

Combined effects of high doses and temperature on radiation-induced radicals and their relative contributions to EPR signal in gamma-irradiated alanine.

Electron Paramagnetic Resonance (EPR) study of irradiated l-alanine showed differences in dose-response curves obtained at low and high microwave power for a broad range of doses, up to 3000 kGy. A mathematical model was fitted to experimental data and calculated yields of generation and of destruction of radicals showed variations with microwave power. The calculations were applied to both double integrals of the total EPR signal and to its components reflecting contributions of radicals R1, R2 and R3 in the alanine EPR signal. The relative contributions of radicals R1, R2 and R3 varied with dose >100 kGy; an increase in relative contribution of R3 was accompanied by a decrease in contribution of R1 radicals. The observed fading of EPR signal intensity in samples annealed to 175-208 degrees C was a strong function of dose, and varied by 2-3 orders of magnitude in the dose range examined.

Development of physical and numerical techniques of Alanine/EPR dosimetry in radiotherapy.

In this work, a set of 50 alanine dosimeters has been used in a radiotherapy context, simulating a two-dimensional treatment in a non-overlapping dosimeter configuration. The dose is reconstructed from physical and numerical simulation of the electron paramagnetic resonance signal, calculating the spin density. Thus, it can be used to better adjust the error in the calibration curve to give a final accuracy of <0.03 Gy. A complete set of experimental test parameters have been used with a standard dosimeter in order to obtain the best analysis configuration. These results indicate that for a conventional treatment of some hundreds of mGy, this method can be useful with a correct signal validation. A numerical test and fitting software has been developed. The general use of alanine/electron paramagnetic resonance dosimetry in radiotherapy context is discussed.

EPR/alanine dosimetry in LDR brachytherapy--a feasibility study.

In this study, we present the results of in vivo dosimetry, using electron paramagnetic resonance in l-alanine, performed on 13 patients treated for gynaecological cancers. The doses from (137)Cs (12 samples) and (192)Ir (one sample) brachytherapy sources were determined inside vagina. The detectors had a form of small cellulose capsules tightly filled with crystalline alanine. The positions of the detectors were reconstructed from two orthogonal radiographs. The planned doses were calculated with a computer planning system (PLATO, Nucletron). The relative deviations between planned and measured doses ranged from -23 to +14%. The mean deviation from the prescribed dose was relatively low (-5%) with SD of 10%. The main sources of differences between the measured and calculated doses were attributed to uncertainty in the determination of the detector position inside the patient's body and to uncontrolled changes in the detector position during the treatment.

Ir-192 HDR transit dose and radial dose function determination using alanine/EPR dosimetry.

Source positioning close to the tumour in high dose rate (HDR) brachytherapy is not instantaneous. An increment of dose will be delivered during the movement of the source in the trajectory to its static position. This increment is the transit dose, often not taken into account in brachytherapeutic treatment planning. The transit dose depends on the prescribed dose, number of treatment fractions, velocity and activity of the source. Combining all these factors, the transit dose can be 5% higher than the prescribed absorbed dose value (Sang-Hyun and Muller-Runkel, 1994 Phys. Med. Biol. 39 1181-8, Nath et al 1995 Med. Phys. 22 209-34). However, it cannot exceed this percentage (Nath et al 1995). In this work, we use the alanine-EPR (electron paramagnetic resonance) dosimetric system using analysis of the first derivative of the signal. The transit dose was evaluated for an HDR system and is consistent with that already presented for TLD dosimeters (Bastin et al 1993 Int. J. Radiat. Oncol. Biol. Phys. 26 695-702). Also using the same dosimetric system, the radial dose function, used to evaluate the geometric dose degradation around the source, was determined and its behaviour agrees better with those obtained by Monte Carlo simulations (Nath et al 1995, Williamson and Nath 1991 Med. Phys. 18 434-48, Ballester et al 1997 Med. Phys. 24 1221-8, Ballester et al 2001 Phys. Med. Biol. 46 N79-90) than with TLD measurements (Nath et al 1990 Med. Phys. 17 1032-40).

An experimental and Monte Carlo investigation of the energy dependence of alanine/EPR dosimetry: II. Clinical electron beams.

The energy dependence of alanine/EPR dosimetry for 8, 12, 18 and 22 MeV clinical electron beams was investigated by experiment and by Monte Carlo simulations. Alanine pellets in a waterproof holder were irradiated in a water phantom using an Elekta Precise linear accelerator. The dose rates at the reference point were determined following the TG-51 protocol using an NACP-02 parallel-plate chamber calibrated in a (60)Co beam. The EPR spectra of irradiated pellets were measured using a Bruker EMX 081 EPR spectrometer. Experimentally, we found no significant change in alanine/EPR response to absorbed dose-to-water over the energy range 8-22 MeV at an uncertainty level of 0.6%. However, the response for high-energy electrons is about 1.3 (+/-1.1)% lower than for (60)Co. The EGSnrc Monte Carlo system was used to calculate the ratio of absorbed dose-to-alanine to absorbed dose-to-water and it was shown that there is 1.3 (+/-0.2)% reduction in this ratio from the (60)Co beam to the electron beams, which confirms the experimental results. Alanine/EPR response per unit absorbed dose-to-alanine was also investigated and it is the same for high-energy electrons and (60)Co gamma-rays.