Massimo Pinto

Future development of biologically relevant dosimetry

Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented.

Investigation of adaptive responses in bystander cells in 3D cultures containing tritium-labeled and unlabeled normal human fibroblasts.

Abstract The study of radiation-induced bystander effects in normal human cells maintained in three-dimensional (3D) architecture provides more in vivo-like conditions and is relevant to human risk assessment. Linear energy transfer, dose and dose rate have been considered as critical factors in propagating radiation-induced effects. This investigation uses an in vitro 3D tissue culture model in which normal AG1522 human fibroblasts are grown in a carbon scaffold to investigate induction of a G1 arrest in bystander cells that neighbor radiolabeled cells. Cell cultures were co-pulse-labeled with [3H]deoxycytidine (3HdC) to selectively irradiate a minor fraction of cells with 1–5 keV/µm β particles and bromodeoxyuridine (BrdU) to identify the radiolabeled cells using immunofluorescence. The induction of a G1 arrest was measured specifically in unlabeled cells (i.e. bystander cells) using a flow cytometry-based version of the cumulative labeling index assay. To investigate the relationship between bystander effects and adaptive responses, cells were challenged with an acute 4 Gy γ-radiation dose after they had been kept under the bystander conditions described above for several hours, and the regulation of the radiation-induced G1 arrest was measured selectively in bystander cells. When the average dose rate in 3HdC-labeled cells (<16% of population) was 0.04–0.37 Gy/h (average accumulated dose 0.14–10 Gy), no statistically significant stressful bystander effects or adaptive bystander effects were observed as measured by magnitude of the G1 arrest, micronucleus formation, or changes in mitochondrial membrane potential. Higher dose rates and/or higher LET may be required to observe stressful bystander effects in this experimental system, whereas lower dose rates and challenge doses may be required to detect adaptive bystander responses.

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.

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.

A graphite calorimeter for absolute measurements of absorbed dose to water: application in medium-energy x-ray filtered beams

The Italian National Institute of Ionizing Radiation Metrology (ENEA-INMRI) has designed and built a graphite calorimeter that, in a water phantom, has allowed the determination of the absorbed dose to water in medium-energy x-rays with generating voltages from 180 to 250 kV. The new standard is a miniaturized three-bodies calorimeter, with a disc-shaped core of 21 mm diameter and 2 mm thickness weighing 1.134 g, sealed in a PMMA waterproof envelope with air-evacuated gaps. The measured absorbed dose to graphite is converted into absorbed dose to water by means of an energy-dependent conversion factor obtained from Monte Carlo simulations. Heat-transfer correction factors were determined by FEM calculations. At a source-to-detector distance of 100 cm, a depth in water of 2 g cm(-2), and at a dose rate of about 0.15 Gy min(-1), results of calorimetric measurements of absorbed dose to water, D(w), were compared to experimental determinations, D wK, obtained via an ionization chamber calibrated in terms of air kerma, according to established dosimetry protocols. The combined standard uncertainty of D(w) and D(wK) were estimated as 1.9% and 1.7%, respectively. The two absorbed dose to water determinations were in agreement within 1%, well below the stated measurement uncertainties. Advancements are in progress to extend the measurement capability of the new in-water-phantom graphite calorimeter to other filtered medium-energy x-ray qualities and to reduce the D(w) uncertainty to around 1%. The new calorimeter represents the first implementation of in-water-phantom graphite calorimetry in the kilovoltage range and, allowing independent determinations of D(w), it will contribute to establish a robust system of absorbed dose to water primary standards for medium-energy x-ray beams.

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).

Analysis of Radiation-Induced Chromosomal Aberrations on a Cell-by-Cell Basis after Alpha-Particle Microbeam Irradiation: Experimental Data and Simulations

There is a continued need for further clarification of various aspects of radiation-induced chromosomal aberration, including its correlation with radiation track structure. As part of the EMRP joint research project, Biologically Weighted Quantities in Radiotherapy (BioQuaRT), we performed experimental and theoretical analyses on chromosomal aberrations in Chinese hamster ovary cells (CHO-K1) exposed to α particles with final energies of 5.5 and 17.8 MeV (absorbed doses: ∼2.3 Gy and ∼1.9 Gy, respectively), which were generated by the microbeam at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. In line with the differences in linear energy transfer (approximately 85 keV/μm for 5.5 MeV and 36 keV/μm for 17.8 MeV α particles), the 5.5 MeV α particles were more effective than the 17.8 MeV α particles, both in terms of the percentage of aberrant cells (57% vs. 33%) and aberration frequency. The yield of total aberrations increased by a factor of ∼2, although the increase in dicentrics plus centric rings was less pronounced than in acentric fragments. The experimental data were compared with Monte Carlo simulations based on the BIophysical ANalysis of Cell death and chromosomal Aberrations model (BIANCA). This comparison allowed interpretation of the results in terms of critical DNA damage [cluster lesions (CLs)]. More specifically, the higher aberration yields observed for the 5.5 MeV α particles were explained by taking into account that, although the nucleus was traversed by fewer particles (nominally, 11 vs. 25), each particle was much more effective (by a factor of ∼3) at inducing CLs. This led to an increased yield of CLs per cell (by a factor of ∼1.4), consistent with the increased yield of total aberrations observed in the experiments.

Radiological and Nuclear Events: Challenges, Countermeasures and Future Perspectives

Over the last few years a broad array of organizations have practiced terrorism with the aim to achieve political, criminal, religious, and ideological goals. These acts have revitalized awareness of the threat of attacks involving chemical, biological, radiological or nuclear weapons. In particular radiological and nuclear methods are likely to be pursued by well organised terrorist groups, particularly those which have access to financial resources. The objective of this paper is to provide the reader with basic knowledge of possible radiological and nuclear events and the potential risks they pose. The document focuses on the characteristics of radiologic and nuclear agents as well as on the basics of response. Ultimately, this article explores how emerging technology has been infusing additional complexity into the global radiological and nuclear threat scenario.

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.

Broadcasting in the Airways: The Fifth Anniversary of the Radiation Research Podcast1

The Radiation Research Podcast was funded just over five years ago by a few Radiation Research Society members. To date, the volunteers running the podcast have produced and published online, open access, over 70 audio interviews. The program includes monthly interviews with authors of articles, award winners, and other recordings at conferences, such as round table discussions. We here present an overview of the podcast, from its creation to its fifth birthday, to explain how it is working, how the featured interviews are scheduled, and what future directions are taken. So, stay tuned!