This thesis presents measurements of charged current deep inelastic scattering cross sections in e+p collisions with longitudinally polarised positron beams. The measurements are based on data taken by the ZEUS detector at the HERA collider during the 2006-2007 run- ning period. The data sample has an integrated luminosity of 132 pb-1 and was taken at a centre-of-mass energy of 318 GeY. The total cross section has been measured at positive and negative values of the longitu- dinal polarisation of the positron beam (Pe). In addition, the single differential cross sections dδ / dQ2, dδ / dx and dδ / dy have been measured for Q2 > 200 Ge y2, also using both positively and negatively polarised positron beams. The reduced cross section has been measured in nine bins of Q2 in the kinematic range 280 < Q2 < 30000 Gey2 and 0.0078 < x < 0.42. The results are compared against the descriptions provided by the CTEQ6.6, MSTW 2008, HEARPDF1.0 and ZEUS-JETS PDFs. In general, the measured cross sections are well described by these predictions. Based on the measurement of the total cross section as a function of the polarisation of the positron beam, a lower limit on the mass of a hypothetical right-handed W boson has been extracted from the upper limit of the cross-section at Pe = -1. This limit is complementary to the limits obtained from direct searches (for example at CDF and D0) because the limit presented herein is for a space-like vV, whereas for direct searches, the limit on the mass of a time-like W boson is obtained. The results of this analysis have been published and have been included ill the determination of the HERAPDF theoretical prediction and also in HI and ZEUS combined results.

Fluorine-18 Fluorodeoxyglucose positron emission tomography-computed tomography (F-18 FDG PET-CT) is now established in the staging, restaging and therapy response monitoring of Hodgkin’s lymphoma (HL) and high grade Non-Hodgkin’s lymphoma (HG NHL), specifically for nodal disease and extra-nodal disease excluding the bone marrow. The role of FDG PET-CT for evaluating bone marrow involvement in HL and HG NHL has not been established yet. There are however several publications on this subject but no consensus has been reached. Bone marrow trephine biopsy (BMB) is the gold standard for bone marrow assessment in lymphoma. Although the occurrence of adverse effects is uncommon, BMB is an invasive procedure that may induce anxiety in patients. A retrospective review of FDG PET-CT bone marrow findings of HL patients referred for a staging scan from June 2008 to January 2014 was done, these findings were compared to the BMB findings also done as part of initial staging. The findings of 55 patients were reviewed analysed.

The work presented involved simulation and experimental studies aimed at improving the methodology of positron annihilation lifetime spectroscopy (PALS), and applied PALS to gain a better understanding of doping mechanisms in ABO3 perovskite oxide materials. Reliable decomposition of PALS spectra requires an accurate description of the instrument resolution function (IRF) and the extrinsic, source component, annihilation events. The source terms include annihilations with the crystallites of the radionuclide and in the thin foil normally used to support the source. In principle both the IRF and the source correction terms can accurately be determined if samples exhibiting a true single lifetime component are measured. A series of annealing studies was performed on commercially available high purity polycrystalline metal samples to reduce the defect concentration below the approximate 0.1 ppm detection limit of PALS. The study showed that despite the numerous reports in literature it was not possible to reproduce the results with similar annealing conditions or sample purity. The possibility of utilising two-lifetime materials to enable the extraction of source correction terms is analysed using simulations, and by experiments on commercially available pure polycrystalline metals. The positron source is commonly deposited on, and supported by, a thin Kapton foil. As part of this work variable energy PALS (VE-PALS) performed at the Munich Research Reactor FRMII on Kapton foils were analysed. This enabled one of the source correction terms to be unambiguously determined. In consequence, the source correction terms for a Kapton supported positron source were extracted from measurements using annealed nickel exhibiting two positron lifetime components. PALS was applied to a study on donor doping of PbTiO3 ceramics using a series of lanthanide-ions. It has been proposed that the smaller Ln-ions may act as amphoteric dopants substituting either on the A-site as a donor, or on the Bsite as an acceptor. In this study Ln-ions in size from La down to Er were studied. A systematic variation in the average positron lifetime was observed where the value was constant from La to Gd and then reduced for the smaller ions. The decrease in average lifetime provides evidence for a reduction in the fraction of trapping to A-site related vacancy defects. The onset of a reduction in the average lifetime between Gd and Dy provides evidence for a change in the doping mechanism resulting in a relative reduction in the fraction of A-site vacancy positron trapping. In contrast to PbTiO3, donor doping of SrTiO3 normally results in electron charge compensation. Recently this has been very clearly demonstrated for La3+ doped SrTiO3 thin films grown by molecular beam epitaxy (MBE) which exhibit exceptional electron mobilities. A series of MBE films grown at University of California Santa Barbara were measured by VE-PALS at FRMII and have been analysed here. Strontium vacancies were identified, and a reduced bulk lifetime component was also observed. This enabled bulk lifetime values to be obtained from two of the films which were in good agreement with the previously obtained values from single crystal samples. A PALS study was also performed on a series of B-site donor, Nb, doped SrTiO3 crystals. High intensity reduced bulk components were observed and enabled measurements of the bulk lifetime. The highest Nb doping level samples showed the most intense reduced bulk lifetime but also clearly demonstrated the presence of Sr vacancies. The observation of A-site vacancy defects for both Nb-doped and La-doped SrTiO3 suggest that formation of these defects is preferred and are independent of the site of incorporation of the donor ion. Studies were also performed on acceptor doped SrTiO3. PALS measurements were made on a series of Fe-doped SrTiO3 ceramic samples, and VE-PALS measurements on pulsed laser deposition of Fe-doped SrTiO3 thin film samples were analysed. The positron lifetime measurements on the ceramic samples showed a dominant 166(3) ps component, a value less than the Ti-vacancy lifetime. It is proposed that the component contains a contribution from positrons trapping at oxygen vacancy substitutional Fe impurity complexes with a local charge that is neutral or negative. The measurements on the series of Fe-doped PLD SrTiO3 films suggest a complex relation between the vacancy defect content of a film and both the Fe-doping and PLD growth conditions. Films grown with higher laser fluence values contained Sr vacancy defects, in contrast to previous studies of acceptor doped perovskites. Films grown with low laser fluence or with high Fe-content showed dominant trapping to Ti-vacancy related defects.

Hypoxia is one of the hallmarks of cancer. It was first postulated to occur in solid tumours by Thomlinson and Gray in 1955.1 The presence of hypoxia has been demonstrated in different types of solid tumours.2 Intratumoral hypoxia is caused by the lack of functional blood vessels in proliferating tumour tissue, resulting in low intratumoral oxygen concentrations. If hypoxia is severe or prolonged, cell death occurs.3 Malignant cells can undergo genetic and adaptive changes that allow them to escape from dying of oxygen deprivation. These changes are associated with a more aggressive malignant phenotype 4,5 conferring resistance to radiation 6,7 and chemotherapeutic agents.3,8,9 Hence hypoxia is known to be a key factor responsible for tumour resistance in humans. / Invasive polarographic oxygen sensor measurements have demonstrated hypoxia in solid tumours and it is generally defined to occur at an oxygen tension less than ten mmHg.10 Perhaps of more importance is that hypoxia has been demonstrated to be a prognostic indicator for local control after treatment with radiotherapy in glioma, head and neck and cervical cancers.11-13 It has also been able to predict for survival and the presence of distant metastases in soft tissue sarcomas.14 Finally, the significance of hypoxia in the activation and induction of functional molecules such as hypoxia inducible factors (HIFs) and VEGF, the modulation of gene expression (e.g. carbonic anhydrase IX), increased proto-oncogene levels, activation of nuclear factors and accumulation of other proteins (e.g. TP53) although progressing, is yet to be defined.15,16 / Thus, it is of clinical interest to understand the levels of hypoxia and numbers of hypoxic cell populations in tumours, particularly those resistant to radiation and chemotherapy. In doing so clinicians and researchers may formulate more accurate prognostic information and develop treatments targeting hypoxic cells. Renal cell carcinoma (RCC) is a tumour resistant to radiation and chemotherapy that is yet to have its oxygen status investigated. / Although the “gold standard” of oxygen tension measurement is the Polarographic Oxygen Sensor (POS or Eppendorf pO2 histograph), non-invasive means of measuring oxygen status via imaging, immunohistochemistry or serum tumour markers are more practical. As highlighted by Menon and Fraker, it is imperative that reliable, globally usable, and technically simplistic methods be developed to yield a consistent, comprehensive, and reliable profile of tumour oxygenation. Until newer more reliable techniques are developed, existing independent techniques or appropriate combinations of techniques should be optimized and validated using known endpoints in tumour oxygenation status and/or treatment outcomes.17 / Hanahan and Weinberg 18 surmised that the field of cancer research has largely been guided by a reductionist focus on cancer cells and the genes within them- a focus that has produced an extraordinary body of knowledge. Looking forward in time, they believe that progress in cancer research would come from regarding tumours as complex tissues in which mutant cancer cells have conscripted and subverted normal cell types (endothelial cells, immune cells, fibroblasts) to serve as active collaborators in their neoplastic agenda. The interactions between the genetically altered malignant cells and these supporting coconspirators will prove critical to understanding cancer pathogenesis and to the development of novel, effective therapies.18 / Essentially, the background outlined here not only highlights the core aim of this thesis: to better understand the oxygen status of renal cell carcinoma and the relationship of this to angiogenesis so that better targeted therapies may be pursued in the future; but it also places this research in the context of the future proposed by Hanahan and Weinberg,18 by clearly focusing on collaborators in the neoplastic agenda, rather than just tumour cells themselves, to better understand RCC.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

<p>Positron Emission Tomography (PET) has gained an important roll in clinical for diagnosis, staging and prognosis of a range of cancer types. Utilization of PET for monitoring and evaluation of cancer treatment is an attractive but almost new concept. The proper choice of PET-tracer as a biomarker for treatment follow-up is crucial. The important characteristic for a suitable tracer is its ability to reflect the response to a treatment at an early stage, before any morphologically changes occurs. It would be an advantage to screen a battery of PET tracers in a preclinical model and introduce a few potential tracers in clinical trial. </p><p>The most conventional pre-clinical approach in PET-oncology utilizes xenografts in mice or rats and requires a large number of subjects. It would be a great advantage to introduce a less demanding but still reliable preclinical method for a more efficient planning of studies in animal model and then in human trials. </p><p>The Multicellular Tumour Spheroid (MTS) system represents an intermediary level between cells growing as monolayer and solid tumours in experimental animals or patients. It mimics the growth of naturally occurring human tumours before neovascularization and appears to be more informative than monolayer and more economical and more ethical than animal models.</p><p>The aim of this work was to establish, refine and evaluate the application of MTS model as a preclinical approach in PET oncology. The vision was to introduce a preclinical method to probe and select PET tracer for treatment monitoring of anticancer drugs, which can hopefully be applied for optimization in breast cancer treatment.</p><p>In this thesis, a number of basic experiments were performed to explore the character of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) uptake in MTS. FDG as the most established PET tracer was an obvious initial option for the evaluation of the model. For further assess-ment, we studied effects on FDG uptake in MTS treated with five routinely used chemother-apy agents. For association of PET tracer uptake to size change of MTS, we developed a reliable and user-friendly method for size determination of MTS. The next step was to apply the MTS model to screen PET tracers for analysis of early response of chemotherapy in breast cancer. Finally the method was utilized for translational imaging exemplified with a new chemotherapy agent.</p><p>The results were encouraging and the MTS model was introduced and evaluated as a preclini-cal tool in PET oncology. The method was implicated to in vitro quickly assess a therapy profile of existing and newly developed anticancer drugs in order to investigate the effects of candidate drugs on tumour-growth, selection of appropriate PET tracer for treatment monitor-ing and finally understanding relation between growth inhibition and biomarkers as part of translational imaging activities.</p>

Positron emission tomography (PET) tracer 3-fluoro-3-deoxythymidine (FLT) is used for imaging tumor proliferation. Prior to this work, human equilibrative nucleoside transporter 1 (hENT1) was the only known human nucleoside transporter (hNT) capable of FLT transport. The aim of this research was to determine if other hNTs, including hENT2, human concentrative nucleoside transporter 1 (hCNT1), hCNT2 and hCNT3, were capable/important of/for FLT transport in mammalian cells. Transport assays performed in Xenopus laevis oocytes producing recombinant hNTs demonstrated that hENT1/2 and hCNT1/3 were capable of FLT transport. FLT uptake assays with or without hENT1 inhibitor nitrobenzylmercaptopurine ribonucleoside (NBMPR) in various cultured cancer cell lines demonstrated that hENT1 was responsible for the majority of mediated FLT uptake in all tested cell lines, suggesting that hENT1 was important for FLT uptake. The in vivo role of hENT1 in FLT uptake was determined by performing [18F]FLT PET on wild-type and ENT1 knockout mice. One hour after [18F]FLT injection, ENT1 knockout mice displayed significantly reduced [18F]FLT accumulation in the blood, heart, brain, kidney, liver, and lungs compared to wild-type mice. Interestingly, ENT1 knockout mice displayed increased [18F]FLT accumulation in the bone marrow and spleen which both have high CNT expression, suggesting that loss of ENT1 significantly alters FLT biodistribution in mice. hENT1 is a predictive marker of gemcitabine response in pancreatic cancers. Since FLT uptake and gemcitabine toxicity are dependent on hENT1, FLT uptake may predict gemcitabine response in pancreatic cancers. To test this hypothesis, six different pancreatic cancer cell lines were analyzed for FLT uptake and gemcitabine toxicity. hENT1/2 inhibition in cells decreased FLT uptake and gemcitabine sensitivity. In five of six cell lines, a positive correlation was observed between FLT uptake and gemcitabine toxicity, suggesting that FLT PET may be clinically useful for predicting gemcitabine response in pancreatic cancers. The results from this research suggest that hNTs, especially hENT1, are important for FLT uptake in mammalian cells and that FLT uptake can predict gemcitabine response in most cultured pancreatic cancer cells. The results warrant FLT PET clinical trials in pancreatic cancer patients to determine the potential of FLT PET in predicting gemcitabine response.

Positron Emission Tomography (PET) has gained an important roll in clinical for diagnosis, staging and prognosis of a range of cancer types. Utilization of PET for monitoring and evaluation of cancer treatment is an attractive but almost new concept. The proper choice of PET-tracer as a biomarker for treatment follow-up is crucial. The important characteristic for a suitable tracer is its ability to reflect the response to a treatment at an early stage, before any morphologically changes occurs. It would be an advantage to screen a battery of PET tracers in a preclinical model and introduce a few potential tracers in clinical trial. The most conventional pre-clinical approach in PET-oncology utilizes xenografts in mice or rats and requires a large number of subjects. It would be a great advantage to introduce a less demanding but still reliable preclinical method for a more efficient planning of studies in animal model and then in human trials. The Multicellular Tumour Spheroid (MTS) system represents an intermediary level between cells growing as monolayer and solid tumours in experimental animals or patients. It mimics the growth of naturally occurring human tumours before neovascularization and appears to be more informative than monolayer and more economical and more ethical than animal models. The aim of this work was to establish, refine and evaluate the application of MTS model as a preclinical approach in PET oncology. The vision was to introduce a preclinical method to probe and select PET tracer for treatment monitoring of anticancer drugs, which can hopefully be applied for optimization in breast cancer treatment. In this thesis, a number of basic experiments were performed to explore the character of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) uptake in MTS. FDG as the most established PET tracer was an obvious initial option for the evaluation of the model. For further assess-ment, we studied effects on FDG uptake in MTS treated with five routinely used chemother-apy agents. For association of PET tracer uptake to size change of MTS, we developed a reliable and user-friendly method for size determination of MTS. The next step was to apply the MTS model to screen PET tracers for analysis of early response of chemotherapy in breast cancer. Finally the method was utilized for translational imaging exemplified with a new chemotherapy agent. The results were encouraging and the MTS model was introduced and evaluated as a preclini-cal tool in PET oncology. The method was implicated to in vitro quickly assess a therapy profile of existing and newly developed anticancer drugs in order to investigate the effects of candidate drugs on tumour-growth, selection of appropriate PET tracer for treatment monitor-ing and finally understanding relation between growth inhibition and biomarkers as part of translational imaging activities.

Because the information advance in technology, the social welfare gradually increase, creates the government expenditure to increase, the finance is difficult. In 2000, the government had announced private participation public construction law, positively impelling the private organization participation public construction, and used the resources, the technology, the efficiency to lighten the government serious financial burden, and created the vigorous folk commercial vitality. The high tech health center is medical industry extending, and is one kind of important tool to impel the preventive medicine. Although it has used the massive medicine theory and the technology, it has not involved the treatment behavior and the medicine prescription. However, it still located in the medical scope, must controlled by the government health organization. At present, the health center has two kinds of managements, one is attached in the hospital, and the other picks the independent form. This case belongs to former. The rehabilitation, operation and transfer on the positron emission tomography center of Kaohsiung Veterans General Hospital bases on the law of private participation public construction. The rehabilitation and operation periods amounts to 11 years. Kaohsiung Veterans General Hospital should suggest that specialized organization or by itself to handle the feasibility and earlier scheme before R.O.T. proposals. If the earlier scheme checks to pass, Veterans General Hospital has to proceed following system of preposition and commercial attraction. Bases on the market analysis, we find that five hospitals have been established positron emission tomography equipment in the area of Kaohsiung and Pingtung. At present, the market supplies increase much, and potential market demands develop slowly. Under these factors disturbance about global budget payment system or hospital excellent project, it inevitably will have the influence on the investment will of industry. Moreover, the condition of industrial and marketable environment, like the supply source of positron medicine FDG, the degree of market development, the medical standard of teams, will be the essential topics. From financial assessment, we find that the private organization participates in the business of the positron emission tomography center of Kaohsiung Veterans General Hospital by the R.O.T. form, Kaohsiung Veterans General Hospital could gain considerable premium, the management efficiency, the higher reputation, and provide the precise health examines. The franchised corporation also could gain required return. The bank financing gets safety. Therefore, the contract about the private participation in the positron emission tomography center of Kaohsiung Veterans General Hospital resembles reasonable. By the sensitivity analysis, we find that the key factors in turn as follows: Revenue, operating cost, operating expenses, initial investment, and financing interest rate. Revenue at their own expense affects this case much higher than customers. Health insurance revenue is regulated by the global budget payment system, we find that pay point is more sensitive than pay value per point, and the franchised corporation must spend more resources to develop the market about non-insurance revenue. The R.O.T. on the positron emission tomography center of Kaohsiung Veterans General Hospital belongs to successful case, its main points including: First, we can use R.O.T. business model to break these constraint of laws and regulations, effectively promote the management elasticity and the overall achievements. Second, the party of the public in the plan and operating stage assigns professionals and continues to participate in the coordination and the management, which is helpful to the project implemented. Third, with the lower premium threshold and the higher surveillance standard, this is helpful to the quality control. Finally, by financial assessment, we can control risk management in advance.

At the Gesellschaft für Schwerionenforschung in Darmstadt a therapy unit for heavy ion cancer treatment has been established in collaboration with the Deutsches Krebsforschungszentrum Heidelberg, the Radiologische Universitätsklinik Heidelberg and the Forschungszentrum Rossendorf. For quality assurance the dual-head positron camera BASTEI (Beta Activity meaSurements at the Therapy with Energetic Ions) has been integrated into this facility. It measures ß+-activity distributions generated via nuclear fragmentation reactions within the target volume. BASTEI has about 4 million coincidence channels. The emission data are acquired in a 3D regime and stored in a list mode data format. Typically counting statstics is two to three orders of magnitude lower than those of typical PET-scans in nuclear medicine. Two iterative 3D reconstruction algorithms based on ISRA (Image Space Reconstruction Algorithm) and MLEM (Maximum Likelihood Expectation Maximization), respectively, have been adapted to this imaging geometry. The major advantage of the developed approaches are run-time Monte-Carlo simulations which are used to calculate the transition matrix. The influences of detector sensitivity variations, randoms, activity from outside of the field of view and attenuation are corrected for the individual coincidence channels. Performance studies show, that the implementation based on MLEM is the algorithm of merit. Since 1997 it has been applied sucessfully to patient data. The localization of distal and lateral gradients of the ß+-activity distribution is guaranteed in the longitudinal sections. Out of the longitudinal sections the lateral gradients of the ß+-activity distribution should be interpreted using a priori knowledge.