No description available.

Polymer gel dosimeters are a three dimensional (3D) dosimetry system that may be conveniently applied for verifying highly conformal radiation therapies where standard dosimetry techniques are insufficient. Polymer gel dosimetry with optical computed tomography (OptCT) can be used to measure spatial dose distributions with high resolution. While long experience with MRI has yielded many studies reporting on experiments involving validation of clinical deliveries using polymer gel dosimeters, there are very few studies of this type where OptCT is used. OptCT is a relatively new technique and consequently has not yet been adopted into the clinical environment. As a result, methods and software tools for integrating OptCT measurements into clinical systems are not available. Previous studies from the Medical Physics research group at the Cancer Centre of Southeastern Ontario (CCSEO) and Queen’s University have therefore been limited to simple deliveries and two dimensional (2D) comparisons. In this thesis various software tools and calibration techniques have been developed to allow comparative analysis between OptCT measurements with dose distributions calculated by treatment planning software. Further, a modification of the γ-evaluation (Low et al. 1998) is presented whereby the vector components of γ are used to identify the sources of disagreement between compared dose distributions. Test simulations of the new γ-tool revealed that individual vector components of γ, as well as the resulting vector field can be used to identify certain types of disagreements between dose distributions: especially spatial misalignments caused by geometric misses. The polymer gel dosimetry tools and analysis software were applied to a clinical validation mimicking a prostate conformal treatment with patient setup correction using image guidance. In one experiment greater than 90 % agreement was found between dose distributions in 4%T 50%C NIPAM/Bis dosimeters (Senden et al. 2006) measured with the Vista OptCT unit and dose distributions calculated by Eclipse treatment planning software. / Thesis (Master, Physics, Engineering Physics and Astronomy) -- Queen's University, 2008-12-18 15:46:33.78

Traditional radiation therapy is limited by the radiotoxic effects on surrounding healthy tissues. This project investigated the use of a gold nanoparticle (AuNP) conjugated to a cell-penetrating peptide (CPP) to increase tumour cell death during radiotherapy by maximizing the cellular import of the gold nanoparticles. ~8300 octaarginine CPPs were coupled per 30 nm AuNP through poly(ethylene glycol) spacers (AuNP-PEG-CPP). The CPPs enhanced the internalization of the AuNPs into three human breast cancer cell lines by a factor >2 as compared to untargeted AuNPs. Cells were treated with AuNP-PEG-CPP for 24 hours, prior to radiotherapy and their long-term proliferation was assessed in clonogenic assays. The increased internalization of AuNPs by the CPPs resulted in greater cell death following exposure to 300 kVp radiotherapy, by a dose enhancement factors between 1.3 and 2.1 depending on the cell line. These findings illustrate the potential of using AuNP-CPPs to enhance radiotherapy in patients.

Traditional radiation therapy is limited by the radiotoxic effects on surrounding healthy tissues. This project investigated the use of a gold nanoparticle (AuNP) conjugated to a cell-penetrating peptide (CPP) to increase tumour cell death during radiotherapy by maximizing the cellular import of the gold nanoparticles. ~8300 octaarginine CPPs were coupled per 30 nm AuNP through poly(ethylene glycol) spacers (AuNP-PEG-CPP). The CPPs enhanced the internalization of the AuNPs into three human breast cancer cell lines by a factor >2 as compared to untargeted AuNPs. Cells were treated with AuNP-PEG-CPP for 24 hours, prior to radiotherapy and their long-term proliferation was assessed in clonogenic assays. The increased internalization of AuNPs by the CPPs resulted in greater cell death following exposure to 300 kVp radiotherapy, by a dose enhancement factors between 1.3 and 2.1 depending on the cell line. These findings illustrate the potential of using AuNP-CPPs to enhance radiotherapy in patients.

No description available.

No description available.

The goal of conformal radiation techniques is to improve local tumour control through dose escalation to target volumes while at the same time sparing surrounding healthy tissue. Respiratory motion is known to be the largest intra-fractional organ motion and the most significant source of uncertainty in treatment planning for chest lesions. A method to account for the effects of respiratory motion is to use four-dimensional radiotherapy. While analytical models are useful, it is essential that the motion problem in radiotherapy is addressed by both modeling as well as experimentally studies so that different obstacles can be overcome before clinical implementation of a motion compensation method. Validation of techniques aimed at measuring and minimizing the effects of respiratory motion require a realistic dynamic deformable phantom for use as a gold standard. In this work we present the design, construction, performance and deformable image registration of a novel breathing, tissue equivalent phantom with a deformable lung that can reproducibly emulate 3D non-isotropic lung deformations according to any real lung-like breathing pattern. The phantom consists of a Lucite cylinder filled with water containing a latex balloon stuffed with dampened natural sponges. The balloon is attached to a piston that mimics the human diaphragm. Nylon wires and Lucite beads, emulating vascular and bronchial bifurcations, were glued at various locations, uniformly throughout the sponges. The phantom is capable of simulating programmed irregular breathing patterns with varying periods and amplitudes. A deformable, tissue equivalent tumour, suitable for holding radiochromic film for dose measurements was embedded in the sponge. Experiments for 3D motion assessment, motion reproducibility as well as deformable image registration and validation are presented using the deformable phantom.

The presence of a moderately strong magnetic field, uniform and static, in the irradiated medium modifies the spatial distribution of events. The imposition of a magnetic field produces elecron helices, characterised by their radii and pitches. The differential and integral distribution of track lengths, corresponding to electrons slowing down in water in a magnetic field, have been computed as function of radii and pitches for 200 kVp X-rays and for ⁶⁰ Co gamma-rays. Theoretical work has shown that the probability of energy deposition in a smaller volume of the absorbing medium has been significantly increased as a result of the presence of a magnetic field during photon irradiation. The distributions of track lengths as function of electron radii and pitches have been studied in strong magnetic fields (1 - 20 Tesla). The trajectories of an electron moving in water for different emission angles (up to π/2) and for magnetic fields of 5 and 10 Tesla, have been computed. The data for stopping powers used in this study, cover electron energies of 30 eV to 1200 keV (initial energy). In the presence of a magnetic field, each electron spiral has enclosed a conical volume. As the magnetic field increases, so the volume enclosed by the spiral decrease resulting in a substantial increase in the number of hits (events) compared with events in the same volume in the absence of a magnetic field. The experimental work started with the study of the characteristics of a spherical walled proportional counter. The frequency density, y.f(y), energy probability density, y^2f(y), distributions and their averages overline Y_F and overline Y_D respectively, have been computed on the basis of the pulse height distribution of low-LET radiation. Gamma rays from ¹³⁷Cs and ⁶⁰Co have been used with and without a magnetic field. Transverse magnetic fields of 0.0304, 0.13, 0.24 and 0.34 Tesla as well as a longitudinal magnetic field of 0.0304 Tesla have been used in microdosimetric measurements. An average sphere diameter of 2 μm has been simulated for the purpose. In the presence of the transverse magnetic fields, an increase of up to ~ 45% and ~ 78% has been obtained in the values of overline Y_F and overline Y_D respectively for ^137Cs gamma rays. For ^60Co gamma rays the values of both overline Y_F and overline Y_D increase by up to about 97%. For the longitudinal magnetic field when compared with the corresponding transversal magnetic field, a substantial increase in the value of overline Y_F has been found for ^137Cs gamma rays and a less significant increase for ^60Co gamma rays. Also, a significant increase in overline Y_D has been obtained for both indirectly ionizing radiations.

IMRT provides unprecedented means to sculpt radiation dose in three-dimensions, pledging potential to improve local disease control via conformal dose escalation as well as better normal tissue sparing via conformal avoidance. In this thesis, the feasibility and practicality of delivering high doses to intelligently-defined multiple tumour sub-volumes is verified for intracranial radiation treatments. The term ‘selective multiple boosting’ (SMB) is adopted for the proposed planning scheme. Physical control over local dose deposition is characterised and quantified through the design of two pseudo-anatomy models. The models show that intra-structural optimisation is easily implemented within a standard IMRT planning module. For concentric, spherical boost volumes, regional dose can be controlled at 10 and 5 mm resolution, where a dose differential of 5 and 3 Gy respectively is readily achievable, whilst incrementally boosting neighbouring volumes is more difficult. The limitations of functional imaging techniques are discussed in this context and resolution issues investigated for magnetic resonance spectroscopic imaging (MRSI). Interpolation experiments show that coarse resolutions are not a barrier to using data effectively for defining boost volumes. However, a need for caution and further research on the interpretation and reproducibility of advanced imaging modalities is highlighted. The idea of a composite or hybrid target volume is presented, consisting of multiple tumour contours delineated on different imaging sequences and amalgamated into a probability map of tumour existence. Software has been written for this purpose and demonstrated viable for SMB planning on real patient data. An IMRT plan evaluation toolbox has also been developed, implementing both existing and novel means of characterising the dosimetry and biological effect of these advanced and complex plans. Whilst it is recognised that further work and understanding is required, it is concluded that SMB is not only feasible but also a valuable pursuit in terms of potential clinical gain.

Monoclonal antibody fragments (Fab') which recognise tumour-associated antigens provide an ingenious means of selectively targeting a therapeutic radionuclide to a tumour for radioimmunotherapy. The radionuclide yttrium-90, a long range β(^-) emitter, was chosen to deliver a sterilising dose of radiation to the tumour. A selection of novel functionalised macrocyclic ligands based on a 1,4,7,10-tetraazacyclododecane skeleton have been synthesised, and the stabilities of their yttrium (III) and gadolinium (III) complexes studied in vitro through association and dissociation measurements, and in vivo through animal biodistribution studies. The radiolabelled complexes do not dissociate in vivo. Maleimides are compounds which are capable of selectively reacting with a thiol of an antibody fragment. Selective functionalisation of one of the yttrium binding macrocyclic ligands with either one or three maleimides has been carried out, and the resulting compounds conjugated to tumour seeking humanised antibody fragments. Subsequent radiolabelling with (^90)Y, gave the desired tumour targeting drug for use in radioimmunotherapy. Acridines are a class of intercalating agents which are capable of reversibly binding to DNA. A maleimide functionalised ligand derivatised with acridine was formed. Conjugation of this compound to antibody fragments capable of entering a tumour cell, may permit drug binding to tumour cell DNA, and thus enhance the targeting efficacy of the radiolabelled conjugate.