M P Toni

Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum

The central dogma of radiation biology, that biological effects of ionizing radiation are a direct consequence of DNA damage occurring in irradiated cells, has been challenged by observations that genetic/epigenetic changes occur in unexposed “bystander cells” neighboring directly-hit cells, due to cell-to-cell communication or soluble factors released by irradiated cells. To date, the vast majority of these effects are described in cell-culture systems, while in vivo validation and assessment of biological consequences within an organism remain uncertain. Here, we describe the neonatal mouse cerebellum as an accurate in vivo model to detect, quantify, and mechanistically dissect radiation-bystander responses. DNA double-strand breaks and apoptotic cell death were induced in bystander cerebellum in vivo. Accompanying these genetic events, we report bystander-related tumor induction in cerebellum of radiosensitive Patched-1 (Ptch1) heterozygous mice after x-ray exposure of the remainder of the body. We further show that genetic damage is a critical component of in vivo oncogenic bystander responses, and provide evidence supporting the role of gap-junctional intercellular communication (GJIC) in transmission of bystander signals in the central nervous system (CNS). These results represent the first proof-of-principle that bystander effects are factual in vivo events with carcinogenic potential, and implicate the need for re-evaluation of approaches currently used to estimate radiation-associated health risks.

A standard dosimetry procedure for 192Ir sources used for endovascular brachytherapy

The experimental dosimetry of a high dose rate (HDR) 192Ir source used for the brachytherapy of peripheral vessels is reported. The direct determination of the reference air kerma rate Kr agrees, within the experimental uncertainty, with the results obtained by a well ionization chamber calibrated at the NIST and the manufacturers certification. A highly sensitive (HS) radiochromic film (RCF), that presents only one active layer, was used for the source dosimetry in a water phantom. The adopted experimental set-up, with the source in its catheter positioned on the RCF plane, seems to have given better accuracy of the RCF optical density measurements. The agreement between the measurement of the dose rate constant DKr (10 mm, pi/2) and the literature data confirmed the coherence of the HS RCF calibration obtained by the kerma in air measurements. The RCF measurements supplied dosimetric information about the dose to water per reference air kerma rate D(r, theta)/Kr along the source transverse bisector axis, the radial dose function g(r) and the anisotropy function F(r, theta). The value D(2 mm, pi/2)/Kr = 22.4 +/- 1.2 cGy h(-1)/(microGy h(-1)) is supplied with a dose uncertainty that is essentially due to the indeterminacy of the source position in the catheter. The data of the radial and anisotropy functions have been compared with Monte Carlo determinations reported in the literature.

Key comparison BIPM.RI(I)-K2 of the air-kerma standards of the ENEA-INMRI, Italy and the BIPM in low-energy x-rays

A key comparison has been made between the air-kerma standards of the ENEA-INMRI, Italy and the BIPM in the low-energy x-ray range. The results show the standards to be in agreement at the level of the standard uncertainty for the comparison of 1.9 parts in 10 3 . No significant trend with radiation quality is observed. The results are analysed and presented in terms of degrees of equivalence, suitable for entry in the BIPM key comparison database.

Determination of the Kwall correction factor for a cylindrical ionization chamber to measure air-kerma in 60Co gamma beams.

The factor Kwall to correct for photon attenuation and scatter in the wall of ionization chambers for 60Co air-kerma measurement has been traditionally determined by a procedure based on a linear extrapolation of the chamber current to zero wall thickness. Monte Carlo calculations by Rogers and Bielajew (1990 Phys. Med. Biol. 35 1065-78) provided evidence, mostly for chambers of cylindrical and spherical geometry, of appreciable deviations between the calculated values of Kwall and those obtained by the traditional extrapolation procedure. In the present work an experimental method other than the traditional extrapolation procedure was used to determine the Kwall factor. In this method the dependence of the ionization current in a cylindrical chamber was analysed as a function of an effective wall thickness in place of the physical (radial) wall thickness traditionally considered in this type of measurement. To this end the chamber wall was ideally divided into distinct regions and for each region an effective thickness to which the chamber current correlates was determined. A Monte Carlo calculation of attenuation and scatter effects in the different regions of the chamber wall was also made to compare calculation to measurement results. The Kwall values experimentally determined in this work agree within 0.2% with the Monte Carlo calculation. The agreement between these independent methods and the appreciable deviation (up to about 1%) between the results of both these methods and those obtained by the traditional extrapolation procedure support the conclusion that the two independent methods providing comparable results are correct and the traditional extrapolation procedure is likely to be wrong. The numerical results of the present study refer to a cylindrical cavity chamber like that adopted as the Italian national air-kerma standard at INMRI-ENEA (Italy). The method used in this study applies, however, to any other chamber of the same type.

Direct determination of the absorbed dose to water from 125I low dose-rate brachytherapy seeds using the new absorbed dose primary standard developed at ENEA-INMRI

Low-intensity radioactive sources emitting low-energy photons are used in the clinic for low dose-rate brachytherapy treatments of tumours. The dosimetry of these sources is based on reference air kerma rate measurements. The absorbed dose rate to water at the reference depth d0?=?1?cm, , is then obtained by a conversion procedure with a large relative standard uncertainty of about 5%. This paper describes a primary standard developed at ENEA-INMRI to directly measure due to LDR sources. The standard is based on a large-angle and variable-volume ionization chamber, embedded in a graphite phantom and operating under ?wall-less air chamber? conditions. A set of correction and conversion factors, based on experiments and Monte Carlo simulations, are determined to obtain the value of Dw,1 cm from measurements of increment of ionization current with increasing chamber volume. The relative standard uncertainty on is 2.6%, which is appreciably lower than the current uncertainty. Characteristics of the standard, its associated uncertainty budget, and some experimental results are given for 125I BEBIG I25.S16.C brachytherapy seeds. Finally, results of the experimental determination of the dose-rate constant ?1 cm, traceable to the Dw,1 cm and the low-energy air kerma ENEA-INMRI standards, are given. The relative standard uncertainty on ?1 cm is 2.9%, appreciably lower than the typical uncertainty (4.8%) of the values available in the literature.

Report on EUROMET.RI(I)-K1 and EUROMET.RI(I)-K4 (EUROMET project no. 813): Comparison of air kerma and absorbed dose to water measurements of 60Co radiation beams for radiotherapy

The results of an unprecedented international effort involving 26 countries are reported. The EUROMET.RI(I)-K1 and EUROMET.RI(I)-K4 key comparisons were conducted with the goal of supporting the relevant calibration and measurement capabilities (CMC) planned for publication by the participant laboratories. The measured quantities were the air kerma (Kair) and the absorbed dose to water (Dw) in 60Co radiotherapy beams. The comparison was conducted by the pilot laboratory MKEH (Hungary), in a star-shaped arrangement from January 2005 to December 2008. The calibration coefficients of four transfer ionization chambers were measured using two electrometers. The largest deviation between any two calibration coefficients for the four chambers in terms of air kerma and absorbed dose to water was 2.7% and 3.3% respectively. An analysis of the participant uncertainty budgets enabled the calculation of degrees of equivalence (DoE), in terms of the deviations of the results and their associated uncertainties. As a result of this EUROMET project 813 comparison, the BIPM key comparison database (KCDB) will include eleven new Kair and fourteen new Dw DoE values of European secondary standard dosimetry laboratories (SSDLs), and the KCDB will be updated with the new DoE values of the other participant laboratories. The pair-wise degrees of equivalence of participants were also calculated. In addition to assessing calibration techniques and uncertainty calculations of the participants, these comparisons enabled the experimental determinations of NDw/NKair ratios in the 60Co gamma radiation beam for the four radiotherapy transfer chambers. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI Section I, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

A Joint Research Project to improve the accuracy in dosimetry of brachytherapy treatments in the framework of the European Metrology Research Programme.

This paper outlines the joint research project “Increasing cancer treatment efficacy using 3D brachytherapy” co-funded in the FP7, according to the iMERA-Plus Grant Agreement No. 217257 between the EC and EURAMET e. V. (European Association of National Metrology Institutes). The project brings together the capabilities of ten major European National Metrology Institutes in the ionizing radiation field and it is focused on the targeted programme “Health”. It aims at establishing across Europe a more accurate metrological basis in brachytherapy by developing methods for the direct measurement of the quantity absorbed dose to water in brachytherapy dosimetry with an uncertainty on the dose delivered to the target volume less than 5% (k=1) at clinical level. In fact, in the current brachytherapy practice, the procedures to determine the absorbed dose imparted to the patient are affected by an uncertainty that could reduce the treatment success. Most of this uncertainty is due to a lacking metrology. No absorbed-dose primary standards are so far available to assure direct traceability in dosimetry of brachytherapy sources. In order to optimize the brachytherapy treatments there is also a need for more accurate dosimetry with high spatial resolution. The present research project is expected to increase the accuracy of brachytherapy to a level comparable to that typical of radiotherapy with external accelerator beams.

Corrigendum: Experimental determination of the dose rate constant for selected 125I- and 192Ir-brachytherapy sources (2012 Metrologia 49 S219–22)

The consensus value for Λ reported in the last column of table 2 should be Λ = 1.012 × 104 not Λ = 1.021 × 104.

Key comparison BIPM.RI(I)-K3 of the air-kerma standards of the ENEA, Italy and the BIPM in medium-energy x-rays

A key comparison has been made between the air-kerma standards of the ENEA, Italy and the BIPM in the medium-energy x-ray range. The results show the standards to be in general agreement at the level of the expanded uncertainty (k = 2) of the comparison of 6.2 parts in 103. The results are analysed and presented in terms of degrees of equivalence, suitable for entry in the BIPM key comparison database. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Key comparison BIPM.RI(I)-K7 of the air-kerma standards of the ENEA-INMRI, Italy and the BIPM in mammography x-rays

A first key comparison has been made between the air-kerma standards of the ENEA-INMRI, Italy and the BIPM in mammography x-ray beams. The results show the standards to be in agreement at the level of the standard uncertainty for the comparison of 4.8 parts in 10 3 . The results are analysed and presented in terms of degrees of equivalence, suitable for entry in the BIPM key comparison database.