S. Onori

Gamma irradiation effects on poly(dl-lactictide-co-glycolide) microspheres

Gamma radiation treatment plays an increasingly important role in the sterilization/sanitization of pharmaceutical products. However, irradiation may affect the stability of the product and thus its safety of use. We investigated the influence of ionizing radiation on modified release microparticulate drug delivery systems made of two types of polylactide-co-glycolide copolymers (PLG): RG 503 and RG 503H; these polymers have identical molecular weights but different chemical structures. The effect of gamma radiation on polymer stability of the raw polymers (P) and related microspheres (Ms) was evaluated. Samples were irradiated at different irradiation doses (5, 15 and 25 kGy) using 60Co as radiation source. The microspheres were prepared using the spray drying technique. Degradation of PLG and related microspheres was evaluated during six months in terms of average molecular weight (Mw) loss by gel permeation chromatography (GPC) and variation in glass transition temperature (Tg) using differential calorimetry (DSC). The presence of free radicals in the product was tested by electron paramagnetic resonance (EPR). Both P and Ms showed a trend in decreasing their Mw at time 0 as a function of irradiation dose. For RG503 the decay in Mw is always negligible for doses below 15 kGy while it is about 10% for 25 kGy. After 150 days Mw decay was 25% in the microspheres and 20% in the raw polymer. It was not possible to evaluate the radiation effect, at different storage times, for RG503H because this polymer resulted to be unstable even in the regular storage conditions without being irradiated. The concentration of radiation-induced free radicals was higher in RG 503H (both P and Ms) and they were more stable than the free radicals species observed in the case of polymer RG 503. Alterations and/or production of new radicals were observed on exposure of RG 503H microspheres to the light. Radiolytic degradation of RG 503 under vacuum is characterized by a prevalence of the chain scission events leading to a decrease of Mw. Some crosslinking can occur mainly in the post irradiation stage through the decay and coupling of the hydrogen abstraction radicals. A hydroperoxydative cycle, whose mechanism is suggested, is generated in the presence of oxygen.

The second international intercomparison on EPR tooth dosimetry

Eighteen international EPR laboratories participated in the second intercomparison programme. Each participant had to prepare enamel samples and evaluate the absorbed dose from molars that were irradiated in vitro in the range 0-1000 mGy. The objective of the programme was to bring together all methods which are currently applied by different laboratories for EPR dose reconstruction and to demonstrate the present state of dosimetry. An overview of the essential features of the different methods is presented. The current accuracy of EPR tooth enamel dosimetry under defined conditions of irradiation is evaluated

Comparison of sample preparation and signal evaluation methods for EPR analysis of tooth enamel.

In dose reconstruction by EPR dosimetry with teeth various methods are applied to prepare tooth enamel samples and to evaluate the dosimetric signal. A comparison of seven frequently used methods in EPR dosimetry with tooth enamel was performed. The participating Institutes have applied their own procedure to prepare tooth enamel samples and to evaluate the dosimetric signal. The precision of the EPR measurement and the dependence of the estimated dosimetric signal with irradiation up to 1000 mGy were compared. The obtained results are consistent among the different methods. The reproducibility of the dosimetric signal and its estimated relation with the absorbed dose was found to be very close for the applied methods with one possible exception.

ESR identification of irradiated antibiotics: cephalosporins

Abstract The ESR technique was tested as a tool to detect antibiotics irradiated for sterilization purposes. Thirteen different cephalosporins, each commercially available, were given a sterilization dose of 25 kGy and then studied by ESR. For 12 out of the 13 samples tested, a specific radiation-induced signal was detected whose time stability allows identification tests. For one cephalosporin (cefaclor), the same signal is present in the irradiated and unirradiated samples. However, identification is still possible due to the high radiation-induced radical concentration and favorable signal time stability.

Sources of uncertainty in therapy level alanine dosimetry

Abstract The various sources of uncertainty in the evaluation of the absorbed dose in the radiotherapy range (0.5–100 Gy) using the ISS alanine/ESR system are analyzed. The results show that the ISS dosimeters are already suitable for low dose evaluation; nevertheless the need of both an improved sample preparation and an ESR signal manipulation procedure is evident.

Radiochromic film dosimetry of a low energy proton beam.

In this work some dosimetric characteristics of MD-55-2 GafChromic films were studied in a low energy proton beam (21.5 MeV) directly in a water phantom. The nonlinearity of the optical density was quantified by a factor P(lin). A correction factor P(en), that accounts for optical density dependence on the energy, was empirically determined. The effects of detector thickness in depth dose measurements and of the film orientation with respect to beam direction were investigated. The results show that the MD-55-2 films provide dose measurements with the films positioned perpendicularly to the proton beam. A dosimetric formalizm is proposed to determine the dose to water at depth d, with films oriented perpendicularly to the beam axis. This formalism uses a calibration factor of the radiochromic film determined directly on the proton beam at a reference depth in water, and the P(lin) factor, that takes into account the nonlinearity of the calibration curve and the P(en) factor that, in turn takes into account the change of proton beam energy in water. The MD-55-2 films with their high spatial resolution and the quasiwater equivalent material are attractive, positioned perpendicularly along the beam axis, for the absolute dose determination of very small beam sizes and modulated proton beams.

Coordinated research efforts for establishing an in international radiotherapy dose intercomparison service based on the alanine/ESR system

Abstract The IAEA has long been active in the field of high-dose standardization. In cooperation with the Gesellschaft fur Umwelt und Gesundheit (GSF), Germany, an International Dose Assurance Service (IDAS) was established based on alanine/ESR dosimetry. This service operates over the range of 100 Gy to 100 kGy and is directed towards industrial radiation processing in IAEA Member States. In complements the IAEA/WHO TLD postal dose intercomparison service for dose assurance in hospital radiotherapy departments. Experience with the alanine high dose service suggests that the alanine dosimeter might provide superior performance to TLD in the therapy dose range. Preliminary test measurements with the participation of GSF/Germany, Istituto Superiore di Sanita/Italy (both providing alanine dosimeters and their evaluation) and IAEA (providing) reference irradiations traceable to BIPM) seems to justify research efforts through an IAEA Coordinated Research Programme (CRP). This CRP, entitled “Therapy Level Dosimetry with the Alanine/ESR System” is presently under set-up. It will include general work common to all assigned/potential contract holders as well as some specific research topics in accordance to individual proposals of each participant.

Alanine dosimetry of proton therapy beams

An analysis of some of the properties of the ESR-alanine dosimetry in therapeutic proton beams is reported. Thin alanine-based detectors (1 and 2 mm thick pellets and 0.25 mm thick films) were tested in a clinical 62 MeV proton beam. The response of the alanine detectors in unmodulated and modulated proton beams was studied in tissue equivalent phantoms. The dose assessed by alanine was compared to the dose provided by a Markus parallel plate ionization chamber, used for reference dosimetry. Experiments in the 5-250 Gy dose range showed linearity of alanine dose response and no significant differences in the alanine response per unit dose to gammas and protons. Agreement within the experimental uncertainties was found between the alanine and the Markus chamber depth dose curves, including the Bragg peak region.

ISS protocol for EPR tooth dosimetry

Abstract The accuracy in Electron Paramagneetic Resonance (EPR) dose reconstruction with tooth enamel is affected by sample preparation, dosimetric signal amplitude evaluation and unknown dose estimate. Worldwide efforts in the field of EPR dose reconstruction with tooth enamel are focused on the optimization of the three mentioned steps in dose assessment. In the present work, the protocol implemented at ISS in the framework of the European Community Nuclear Fission Safety project “Dose Reconstruction” is presented. A combined mechanical–chemical procedure for ground enamel sample preparation is used. The signal intensity evaluation is carried out with powder spectra simulation program. Finally, the unknown dose is evaluated individually for each sample with the additive dose method. The unknown dose is obtained by subtracting a mean native dose from the back-extrapolated dose. As an example of the capability of the ISS protocol in unknown dose evaluation, the results obtained in the framework of the 2nd International Intercomparison on EPR tooth enamel dosimetry are reported.

INFLUENCING FACTORS ON ESR BONE DOSIMETRY

This paper reports on the influence that temperature during irradiation and dose-rate have on the radiation-induced free-radical yield and time stability in non de-proteinized bone. Bone from chicken legs was irradiated in the 253-293 K temperature range and with two different sources (60Co, 0.6 Gy/s and 12 MeV electrons, 6 x 10(6) Gy/s). Temperature influences type and number of radicals, while radical concentration seems to slightly decrease with dose rate.