RESUMEN
The major part of energy deposition of ionizing radiation is caused by secondary electrons, independent of the primary radiation type. However, their spatial concentration and their spectral properties strongly depend on the primary radiation type and finally determine the pattern of molecular damage e.g. to biological targets as the DNA, and thus the final effect of the radiation exposure. To describe the physical and to predict the biological consequences of charged ion irradiation, amorphous track structure approaches have proven to be pragmatic and helpful. There, the local dose deposition in the ion track is equated by considering the emission and slowing down of the secondary electrons from the primary particle track. In the present work we exploit the model of Kiefer and Straaten and derive the spectral composition of secondary electrons as function of the distance to the track center. The spectral composition indicates differences to spectra of low linear energy transfer (LET) photon radiation, which we confirm by a comparison with Monte Carlo studies. We demonstrate that the amorphous track structure approach provides a simple tool for evaluating the spectral electron properties within the track structure. Predictions of the LET of electrons across the track structure as well as the electronic dose build-up effect are derived. Implications for biological effects and corresponding predicting models based on amorphous track structure are discussed.
Asunto(s)
Electrones , Transferencia Lineal de Energía , Radiación Ionizante , Fenómenos Físicos , Método de MontecarloRESUMEN
Dose build-up effects in the entrance channel of proton Bragg curves were investigated in detail by means of simulations and experiments. There are two relevant dose build-up effects. Firstly, the δ-electron build-up effect which takes place in the first few millimeters of the tissue until an equilibrium state of the forward-scattered δ-electrons is reached. Secondly, the target fragment build-up effect that covers the first centimeters in the entrance channel of the proton Bragg curve. These target fragments are created in inelastic interactions of the beam protons with the target nuclei and partially have low kinetic energies and/or high atomic numbers compared to the incident beam protons. Consequently, the target fragments possess high LET values and thus an increased RBE. However, the production cross sections relevant for target fragmentation in ion beam therapy still have large uncertainties. Therefore, in this work target fragmentation was investigated indirectly by measuring low-noise proton Bragg curves with the focus placed on their build-up regions. The measurements clearly show the magnitude and shape of the two different build-up effects. Additionally, with the application of a magnetic filter, it was possible to separate the measurement of the target fragment build-up effect from the δ-electron build-up effect. Corresponding FLUKA Monte Carlo simulations were carried out for the experimental setup. A comparison of the experimental results with the FLUKA predictions enabled the assessment of the precision of FLUKA models, e.g. the δ-electron production models and the nuclear event generators which are responsible for target fragmentation reactions. It could be shown that the relevant models worked well to reproduce both build-up effects.
Asunto(s)
Simulación por Computador , Electrones , Protones , Monitoreo de Radiación/métodos , Método de Montecarlo , Dosis de Radiación , IncertidumbreRESUMEN
We have previously developed two monoclonal antibodies against the Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA1), designated 1H4 and 2B4. Both detect EBNA1 by in situ staining in established EBV-positive tumours, e.g. Hodgkin's lymphoma and nasopharyngeal carcinoma. An association of EBV with other tumours, notably breast carcinomas, has been reported but remains controversial. Using the antibody 2B4, a nuclear protein has been detected in breast carcinomas that were EBV-negative by other methods, suggesting cross-reactivity with a cellular protein. Furthermore, an association of EBV with various other carcinomas has been reported on the basis of 2B4 immunohistochemistry. Here we show that 2B4 also binds to MAGE-4, a cancer testis antigen expressed in a variety of tumour cells, including breast carcinoma, seminoma and EBV-negative cases of Hodgkin's lymphoma. We conclude that the 2B4 antibody is not suitable for the detection of EBV infection but that additional techniques, particularly in situ hybridization for the detection of the EBV-encoded RNAs (EBERs), should be employed to confirm the presence of EBV. Our results add to the evidence indicating that breast cancer is not an EBV-associated disease.