Σκοπός της εργασίας είναι ο σχεδιασμός και έπειτα η υλοποίηση ενός έξυπνου συστήματος ηλεκτρονικής μάθησης στο τομέα της φυσικής της πυρηνικής ιατρικής, το οποίο θα αποτελεί ένα αρχικό βήμα προς τη κατεύθυνση της ιδανικής διδασκαλίας και μάθησης στο τομέα αυτό. Αφού προσδιορίσαμε τους λόγους για την ανάπτυξη ενός συστήματος ηλεκτρονικής μάθησης στη φυσική της πυρηνικής ιατρικής, αναλύσαμε το κοινό στο οποίο αυτό απευθύνεται, καθορίσαμε συγκεκριμένους μαθησιακούς στόχους, και έχοντας λάβει υπόψη τις στρατηγικές που έχουν εφαρμοστεί μέχρι τώρα στην ηλεκτρονική μάθηση καθώς και τις ιδιαιτερότητες του τομέα της φυσικής της πυρηνικής ιατρικής, σχεδιάσαμε ένα σύστημα ηλεκτρονικής μάθησης, το οποίο περιέχει κατάλληλα εκπαιδευτικά εργαλεία για την επίτευξη του επιθυμητού μαθησιακού αποτελέσματος, καθώς και εργαλεία για την αξιολόγηση του εκπαιδευομένου. Έπειτα προχωράμε στο κτίσιμο της πλατφόρμας. / Aim of this subject is the planning and then the implementation of a “clever” e-learning system in the sector of physics of nuclear medicine, which will constitute an initial step to the direction of ideal teaching and learning in this sector. After we determined the reasons for the development of an e-learning system in the physics of nuclear medicine, analyzed the audience that this is addressed, determined specific learning objectives, and keeping in mind the strategies that have been applied up to now in the e-learning, as well as the particularities of the sector of physics of nuclear medicine, we have designed an e-learning system which contains suitable educational tools for the achievement of desirable learning result as well as tools for learner assessment .Then we proceeded to the building of the platform.

The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast cancers (BCs) and confers an aggressive tumour phenotype with a poor prognosis. Trastuzumab (Herceptin®) is a humanized IgG1 monoclonal antibody (mAb) approved for treatment of HER2-positive breast cancer (BC), however many eligible patients do not respond. The hypothesis was that molecular imaging strategies that probe: i) the expression of HER2; ii) one of the mechanisms of action of trastuzumab or iii) evaluate the viability of tumour cells by their glucose utilization would be useful in predicting and monitoring the response of BC to treatment with trastuzumab. The relationship between tumour HER2 density, uptake of 111In-DTPA-trastuzumab and response to trastuzumab was evaluated by gamma camera imaging, biodistribution studies and monitoring tumour growth in mice implanted with BC xenografts. There was a non-linear relationship between HER2 expression and uptake of this radiopharmaceutical when tumour uptake was corrected for non-specific IgG accumulation and/or circulating blood radioactivity (r2=0.87-0.99). Tumour response corresponded better with the uncorrected tumour uptake of 111In-DTPA-trastuzumab. HER2 downregulation, a putative mechanism of action of trastuzumab, was noted as decreased tumour uptake on microSPECT/CT of mice bearing MDA-MB-361 xenografts administered 111In-DTPA-pertuzumab. Tumour uptake of 111In-DTPA-pertuzumab was reduced by 53% in mice treated for 3 days with trastuzumab (P<0.05) associated with an early molecular response to the drug. Furthermore, tumour uptake of 111In-DTPA-pertuzumab was reduced by 78% (P<0.001) in mice treated for 3 weeks, which corresponded with a reduction in HER2-positive tumour cells, indicating a therapeutic response. The relationship between changes in tumour uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and response to trastuzumab was examined in mice bearing MDA-MB-361 and MDA-MB-231 BC xenografts, with high or very low HER2 expression, treated with trastuzumab. MicroPET imaging and biodistribution studies detected a 43-60% (P<0.03) reduction in tumour uptake of 18F-FDG in mice with MDA-MB-361 xenografts, treated with trastuzumab compared to PBS-treated controls. In contrast, there was no change in 18F-FDG uptake in MDA-MB-231 xenografts, that did not respond to trastuzumab. I conclude that molecular imaging is a promising tool for monitoring response of BC to treatment with trastuzumab.

The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast cancers (BCs) and confers an aggressive tumour phenotype with a poor prognosis. Trastuzumab (Herceptin®) is a humanized IgG1 monoclonal antibody (mAb) approved for treatment of HER2-positive breast cancer (BC), however many eligible patients do not respond. The hypothesis was that molecular imaging strategies that probe: i) the expression of HER2; ii) one of the mechanisms of action of trastuzumab or iii) evaluate the viability of tumour cells by their glucose utilization would be useful in predicting and monitoring the response of BC to treatment with trastuzumab. The relationship between tumour HER2 density, uptake of 111In-DTPA-trastuzumab and response to trastuzumab was evaluated by gamma camera imaging, biodistribution studies and monitoring tumour growth in mice implanted with BC xenografts. There was a non-linear relationship between HER2 expression and uptake of this radiopharmaceutical when tumour uptake was corrected for non-specific IgG accumulation and/or circulating blood radioactivity (r2=0.87-0.99). Tumour response corresponded better with the uncorrected tumour uptake of 111In-DTPA-trastuzumab. HER2 downregulation, a putative mechanism of action of trastuzumab, was noted as decreased tumour uptake on microSPECT/CT of mice bearing MDA-MB-361 xenografts administered 111In-DTPA-pertuzumab. Tumour uptake of 111In-DTPA-pertuzumab was reduced by 53% in mice treated for 3 days with trastuzumab (P<0.05) associated with an early molecular response to the drug. Furthermore, tumour uptake of 111In-DTPA-pertuzumab was reduced by 78% (P<0.001) in mice treated for 3 weeks, which corresponded with a reduction in HER2-positive tumour cells, indicating a therapeutic response. The relationship between changes in tumour uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and response to trastuzumab was examined in mice bearing MDA-MB-361 and MDA-MB-231 BC xenografts, with high or very low HER2 expression, treated with trastuzumab. MicroPET imaging and biodistribution studies detected a 43-60% (P<0.03) reduction in tumour uptake of 18F-FDG in mice with MDA-MB-361 xenografts, treated with trastuzumab compared to PBS-treated controls. In contrast, there was no change in 18F-FDG uptake in MDA-MB-231 xenografts, that did not respond to trastuzumab. I conclude that molecular imaging is a promising tool for monitoring response of BC to treatment with trastuzumab.

The objectives of this thesis are to produce radioactive antibody-conjugated gold nanoparticles to improve the efficacy of targeted radionuclide therapy for the treatment of cancer, and to demonstrate that this product can be produced at Texas A&M University. We have proposed a method for determining the distribution of radioactive nuclei per nanoparticle, which is critical for determining radiotherapeutic efficacy. Using the distribution of radioactive nuclei per nanoparticle, we have produced methods for calculating the radiative dose to tissue using nano-improved targeted radionuclide therapy, but more importantly we propose procedures to experimentally determine the efficacy of targeted radionuclide therapy improved by application of radioactive nanomaterials in combination with immunotherapy, nanomaterial cytotoxicity, and other cancer therapies such as chemotherapy. These methods can also be used to determine the efficacy of combinatory treatments as a function of time. Characterization of the antibody-nanoparticle attachment is critical; we have demonstrated successful antibody-nanoparticle conjugation using atomic force microscopy, dynamic light scattering, and agarose gel electrophoresis, providing more conclusive evidence of successful conjugation compared to flow cytometry. We provide a mathematical derivation from basic electron-transport principles which demonstrates the theoretical dosimetric advantages of applying radioactive nanomaterials to targeted radionuclide therapy. The general formulae can be applied to any tumor size, any radionuclide, and any pharmacokinetic nanoparticle distribution throughout the body, ultimately allowing a quick method of approximating the necessary activation time and treatment dosage parameters for a specific patient without burdensome Monte Carlo computational simulations. We further demonstrated that nano-TRT dosage to tumors should be considered as a function of radial position rather than average, as the dose across the tumor may be noticeably non-uniform causing some portions of the tumor to receive (potentially) significantly less dose than average.

The main purpose of this thesis is to encourage the development of bioeffect planning as an experimental tool by which means bioeffect plans may be compared with standard isodose plans. This thesis also addresses the fundamental problems of the derivation of useful biological models for clinical application and the description of tumour and normal tissue parameter values and their variability. Particular emphasis has been placed on comparing the predictive value of the models and parameters against clinical results of fractionated and continuous irradiation either alone or combined.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 160-168). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 160-168). Also available on the Internet.

Thesis (M. Sc.)--Carleton University, 1999. / Also available in electronic format on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on August 14, 2007) Vita. Includes bibliographical references.

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