Cancer therapy with high-energy particles has proved to be beneficial over the last 10 years. Protons are regarded as being more advantageous because of their distinctive physical depth dose distribution that allows dose conformation to the tumor while sparing normal tissue. In this study, the relative biological effectiveness (RBE) values for the 200-MeV clinical proton beam at iThemba LABS were measured at strategic positions along a 5 cm Spread-Out-Bragg-Peak (SOBP). RBE values were evaluated at the initial plateau of the virgin beam (24.2 mm in Perspex), and at the middle part, distal part and distal edge (12.4% max. dose) along the SOBP (depth in Perspex= 161.4, 181.3 and 207.7 mm respectively). Biological systems used were Chinese hamster ovary cells (CHO-Kl) for both cell survival and micronuclei frequencies as well as human T-lymphocytes for micronuclei frequency analysis. (60)^Co y-irradiation served as a reference. Cell survival measurements yielded RBE values of 1.17 at the distal part and 1.62 at the distal edge (12.4 max. dose). For micronuclei analysis, a limiting RBEap+ay value of 1.3 at the distal part was observed. Using T-lymphocytes, RBEap+/ay values calculated were 2.1, 2.7 and 3.2 at the middle part, distal part and distal edge, respectively. These results show an increase in RBE with depth of penetration and are explained by an increase in ionization density at the end of the SOBP. This is influenced by a high fraction of low-energy protons at that position. Protons were found to be most potent per unit dose towards the end as they slow down to a complete stop. It is recommended that an RBE value slightly greater than the current 1.1 be applied in therapy. Also, that the less steep biological effective depth dose curve be taken into account when dose planning. / Thesis (MSc. ARST) North-West University, Mafikeng Campus, 2003

Thesis (M.Sc.) - Carleton University, 2005. / Includes bibliographical references (p. 130-136). Also available in electronic format on the Internet.

Made available in DSpace on 2014-10-09T12:23:50Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:57:10Z (GMT). No. of bitstreams: 1 01103.pdf: 1172103 bytes, checksum: 91bab2b13d660ec6ae7ebd98dbcc08fa (MD5) / Dissertacao (Mestrado) / IEA/D / Faculdade de Medicina Veterinaria e Zootecnia, Universidade de Sao Paulo - FMVZ/USP

Made available in DSpace on 2014-10-09T12:23:50Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:57:10Z (GMT). No. of bitstreams: 1 01103.pdf: 1172103 bytes, checksum: 91bab2b13d660ec6ae7ebd98dbcc08fa (MD5) / Dissertacao (Mestrado) / IEA/D / Faculdade de Medicina Veterinaria e Zootecnia, Universidade de Sao Paulo - FMVZ/USP

Cells experiencing a low oxygen tension show relative resistance to the lethal effects of radiation. It is believed that the effectiveness of the treatment of certain human tumors is hindered by the existence of such radioresistant cells within the tumor. The purpose of this work was to study the drug Ro-07-0582 both for its toxic effects and its ability to preferentially sensitize hypoxic cells to the lethal effects of radiation (radiosensitize). These properties were examined in vitro in two Chinese hamster cell lines, CHO and CH2B2, and also in the mouse tumour cell line EMT6. Ro-07-0582 is shown to have a chemotherapeutic potential in that it demonstrates a very selective toxicity for hypoxic cells after a few hours exposure. It is much less toxic to aerobic cells. These toxic properties were studied extensively, both in hypoxic and aerobic cell suspensions. The measured endpoint was the ability of a cell to multiply and form a colony of 50 or more cells within an allotted incubation time. Hypoxic toxicity was greater at 37°C than at 22°C and was affected by small changes (~30ppm) in 0₂ concentration in the cell suspension. The toxic effects were similar in the three cell lines. The radiosensitizing capability of Ro-07-0582 was determined by measuring the Dose Modifying Factors (DMF's) for various drug concentrations with each cell line. DMF's were calculated by comparison of survival curves for cell suspensions irradiated under hypoxia in the presence of drug with the survival curve for cell suspensions irradiated under hypoxia in the absence of drug. The DMF for the irradiation of aerobic cells in the absence of drug is called the Oxygen Enhancement Ratio (OER) and was approximately 3.0 in all three cell lines. Ro-07-0582 was found to selectively radiosensitize hypoxic cells in suspension with high efficiency. For each cell line, sensitization was observed with drug concentrations as low as 0.1mM, while concentrations of 10mM or greater yielded DMF's within the measured range of OER values. The presence of 1mM Ro-07-0582 during irradiation of hypoxic cells yields a DMF of 1.8. Introduction of the drug before or after irradiation, instead of during irradiation, had little if any effect. Radiosensitization measurements were also carried out at high cell concentrations (cell pellets), where many sensitizers are ineffective. Results showed that the 0582 radiosensitization attained in cell pellets is quite comparable with that attained in dilute suspension. The attributes of Ro-07-0582 as a potential radiosensi-tizer were considered. The sensitization achieved by Ro-07-0582 is very good, and surpasses that of metronidazole, a chemical under study for clinical use. For drug doses necessary to achieve high levels of sensitization the toxicity of Ro-07-0582 to aerobic cells is quite acceptable. The toxicity to hypoxic cells, however, is much increased over the toxicity to aerobic cells, and this may prove to be a useful adjunct to the drug's sensitizing properties in destroying hypoxic tumour cells. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Proton sources driven by high-power lasers are a promising addition to the portfolio of conventional proton accelerators. Regarding particle cancer therapy, where tumours are irradiated with protons or ions, the novel accelerator technology can be particularly beneficial for translational research - the research branch in which results of basic research are transferred to new approaches for the prevention, diagnosis and treatment of cancer. The overarching aim in the thesis at hand was a translational pilot study to irradiate tumours on mice’s ears with laser-accelerated protons while achieving the quality level of conventional proton accelerators. This is the only way to compare the radiobiological data of the novel accelerator technology with those of the established ones. To enable such experiments a predetermined dose distribution according to the radiobiological model’s requirements must be delivered to a sample volume. Ergo, the laser-driven protons have to be transported and shaped after their initial acceleration. Intense laser-driven proton pulses, inherently broadband and highly divergent, pose a challenge to established beamline concepts on the path to application-adapted irradiation field formation, particularly for 3D. This work demonstrates the successful implementation of a highly efficient and tuneable pulsed dual solenoid setup to generate a homogeneous (laterally and in depth) volumetric dose distribution using only a single dose pulse from the broad laser-driven proton spectrum. The experiments using the ALBUS-2S beamline were conducted at the titanium:sapphire high-power laser Draco PW at the Helmholtz-Zentrum Dresden–Rossendorf. The beamline and its model were characterised and verified via independent methods, leading to first experimental studies providing volumetrically homogeneous dose distributions to detector targets as well as tumour and normal tissue in proof-of-concept studies. To perform the mouse pilot study, a new solenoid with cooling capacities was designed, characterised and implemented in the course of this thesis. The combination of the new solenoid and an overall performance improvement of the laser-proton accelerator, enabled the successful conduction of the mouse model study. The results show that laser-accelerated protons induce a comparable tumour growth delay as protons from conventional accelerators. This outcome and the demonstration of the flawless interaction between laser-proton accelerator, beam transport, dosimetry and biology qualify the laser-based accelerator technology for complex studies in translational cancer research. Looking into the future, their unique extremely high intensity renders them of particular interest for the investigation into the ultra-high dose rate regime. There, the so-called FLASH effect shows fewer side effects in normal tissue while maintaining the same effect in the tumour when the target dose is administered in milliseconds rather than minutes, as currently common. The ALBUS-2S setup at Draco PW already provides all necessary conditions to realise irradiation times of around ten nanoseconds in preclinical studies. This significantly expands the parameter space for investigating the FLASH effect and is presented as a proof-of-concept in this thesis.

No description available.

This thesis is intended as an introductory lab manual on the experimental methods using fluorescence microscopy in modern radiobiology research. It is written for those who are unfamiliar with biology research. It first covers the proper use of laboratory equipment and growth of cell cultures in the lab. Subsequent chapters provide overviews of relevant modern experimental techniques for the quantification of radiation induced DNA damage in cells, and detailed protocols for performing these procedures. Techniques covered include immunostaining with fluorescent antibodies, the comet assay, and plasmid DNA transfections. Results of some straightforward experiments using these techniques are presented.

Thesis (M.Sc.-Res.)--University of Wollongong, 2009. / Typescript. Includes bibliographical references: leaf 91-95.

The purpose of this thesis is to present data pertinent to and propose conclusions regarding the coordination of radiobiologic effectiveness (RBE) and linear energy transfer (LET). RBE is a quantity relating the effectiveness of different radiations in causing cell death. LET is a measure of the rate of energy transferred to material by an ionizing particle. This relationship of these values varies for different particles. The reason for this is still inconclusive. The petitioner has made use of a toolkit for Geant4, known as Geant4-DNA, to perform track-structure analysis on a chromosome model. Geant4 is an object-oriented program for the "simulation of the passage of particles through matter" developed by CERN that makes use of Monte Carlo methods and is expanded by Geant4-DNA to handle low-energy electron physics as well as physic-chemical effects. The chromosome model, in this case, has been developed by the petitioner as a nucleus with a basic, uniform distribution of chromatin. Radiation damage to DNA, in the form of aberrations, lesions and strand breaks, can be coordinated to energy deposited or number of ionizations occurring in the target (in this case DNA or chromatin fiber). Certain threshold values have been established as indicate of different types of DNA damage. The ultimate goal of this work is to score these clusters of events against the threshold values to determine the severity of DNA damage. The final comparison of the results for different particles will provide for a better understanding of the RBE-LET relationships by improving the understanding of the underlying nanodosimetric qualities.