OBJETIVO: A imagem molecular de transportadores de dopamina (DAT) oferecer uma informação diferencial na investigação de doenças neurodegenerativas, como a Doença de Parkinson, diante de uma sólida abordagem quantitativa. Porém, são diversos o número de diferentes métodos semiquantitativos aplicados na prática clínica, que nos quais podem produzir resultados distintos quando aplicados por diferentes avaliadores ou condições de avaliação da imagem de SPECT do corpo estriado. Logo, este estudo pode avaliar a acurácia, precisão e reprodutibilidade de diferentes métodos semiquantitativos de imagens de SPECT do corpo estriado. MATERIAIS E MÉTODOS: Foram realizadas 23 aquisições de SPECT utilizando um simulador antropomórfico estriatal preenchido com diferentes concentrações de atividade de 99mTc. A preparação deste simulador estriatal foi realizada a partir de concentrações de atividades nas cavidades de interesse (núcleo caudado, putâmen e corpo estriado) proporcionalmente maiores do que a da cavidade de referência (background). As imagens foram reconstruídas utilizando parâmetros ideais já protocolados. Cinco métodos baseados em ROIs, dedicados para a quantificação de SPECT do corpo estriado foram avaliados: ROIs desenhadas sobre as imagens de SPECT - (A) Manual, ROIs com dimensões padronizadas - (B) método Twobox e (C) método Threebox; e baseado em imagens estruturais (D) MRI e (E) CT. A acurácia de cada método aplicado foi avaliada através do coeficiente de correlação de concordância (CCC), sua precisão utilizando o coeficiente de Pearson e modelos regressão linear, assim como a reprodutibilidade pode ser investigada através de análises de variabilidade intra- e interobservadores. RESULTADOS: Tanto para as cavidades avaliadas de forma individual (Caudado e Putâmen), quanto para o corpo estriado como um todo, todos os métodos aplicados apresentaram um aumento no CCC dos índices quantificados diante de uma diminuição dos valores nominais de preenchimento. Os métodos D e E apresentaram os máximos valores de CCC na avaliação do núcleo caudado _ 0,89 baixo MRI CA CCC ? e _ 0,84 baixo CT CA CCC ? ) e putâmen ( _ 0,86 baixo MRI PU CCC ? e _ 0,82 baixo CT PU CCC ? ). Entretanto, na avaliação do corpo estriado, o método B apresentou a máxima acurácia dentre os cinco aplicados ( _ 0,95 baixo TWOBOX ST CCC ? ). A significante correlação entre os métodos foi evidenciada por um elevado coeficiente de correlação (r > 0.8). Na avaliação da reprodutibilidade intra e interobservadores uma grande variabilidade foi observada na aplicação do método A, principalmente quando aplicada na semiquantificação de baixas concentrações de atividade. Conclusão: Os cinco métodos semiquantitativos de SPECT do corpo estriado, demonstraram ser eficientes na realização de leituras proporcionais dos índices de BPI mesmo quando aplicados a imagens de diferentes concentrações de atividade. Porém, diante de investigações que necessitem de um processo de quantificação mais acurado e visando avaliar putâmen e núcleo caudado de forma isolada, os métodos estruturais (MRI e CT), demonstraram uma crescente eficiência em representar acurados parâmetros semiquantitativos diante da diminuição dos índices nominais de preenchimento. Na investigação de todo o corpo estriado e carente de qualquer informação estrutural, o método TwoBox passa a ser recomendado devido sua melhor performance diante todos os métodos avaliados. / AIM: The molecular image of dopamine transporters (DAT) gives differential information in research of neurodegenerative diseases, such as Parkinson\'s, when properly approached quantitatively. Yet, each method used in clinical routine may give, or not, different results when the quantifications are applied in images of several activity levels. Hence, this study assessed the accuracy, precision and reproducibility of striatum SPECT images semi-quantification methods, based in ROIs. METHODOLOGY: Twenty-three SPECT images were acquisitions of anthropomorphic striatal phantom filled with different activity concentrations of 99mTc. For each acquisition performed, the specific chambers (caudate and putamen chambers) to large chamber (simulating nonspecific background activity) was filled with solutions activity of different specific to nonspecific ratios (10, 8, 6, 4 and 2 to 1). The images were reconstructed by iterative algorithm, corrected to attenuation effects and the extracted values were analyzed by the specific binding ratio (SBR). Five semi-quantification methods for striatum SPECT, using ROIs was assessment: (A) draw freehand ROIs on SPECT image (manual); standard size ROIs: (B) TwoBox and (C) ThreeBox Methods and VOIs using structural images: (D) MRI and (E) CT. Accuracy of methods applied was assessed by concordance correlation coefficient (CCC) and precision by Pearson\'s coefficient and linear regression. RESUlTS: The SBR quantified both to individual specific chambers and striatal chamber analyzed to all methods applied resulted in a CCC increase with decrease of the nominal values used. For lower SBR values, the D and E methods evidenced the maximum values of CCC in assessment of caudate (CCCMRI_CA = 0.89 e CCCCT_CA = 0.84) and putamen (CCCMRI_PU = 0.86 e CCCCT_PU = 0.82). However, striatal assessments the B method highlights a maximum accuracy between all methods applied (CCCTWOBOX_ST = 0.95), for low values of SBR. A high Pearson\'s coefficient was found in the correlation between the all methods, report thereby a good precision between them (r > 0.8). The high ICC and variability values, showed a high reprodutibility intra- and interobserver for B, C and D methods, white the A and E methods presented a high variability between the raters. CONCLUSION: The five semi-quantification methods of striatum SPECT reported a high precision even when applied in images with activity solutions different. Therefore, to research much accurate and need to assessment just caudate or putamen individually the structural methods - MRI and CT - demonstrated progressive improvement in its quantification to reduction nominal fill index. To assessment striatal chamber and in the absence of structural information, the TwoBox method is advisable due to its excellent agreement with all nominal values when compared to the various semi-quantitative methods investigated. Keywords:

OBJETIVO: A imagem molecular de transportadores de dopamina (DAT) oferecer uma informação diferencial na investigação de doenças neurodegenerativas, como a Doença de Parkinson, diante de uma sólida abordagem quantitativa. Porém, são diversos o número de diferentes métodos semiquantitativos aplicados na prática clínica, que nos quais podem produzir resultados distintos quando aplicados por diferentes avaliadores ou condições de avaliação da imagem de SPECT do corpo estriado. Logo, este estudo pode avaliar a acurácia, precisão e reprodutibilidade de diferentes métodos semiquantitativos de imagens de SPECT do corpo estriado. MATERIAIS E MÉTODOS: Foram realizadas 23 aquisições de SPECT utilizando um simulador antropomórfico estriatal preenchido com diferentes concentrações de atividade de 99mTc. A preparação deste simulador estriatal foi realizada a partir de concentrações de atividades nas cavidades de interesse (núcleo caudado, putâmen e corpo estriado) proporcionalmente maiores do que a da cavidade de referência (background). As imagens foram reconstruídas utilizando parâmetros ideais já protocolados. Cinco métodos baseados em ROIs, dedicados para a quantificação de SPECT do corpo estriado foram avaliados: ROIs desenhadas sobre as imagens de SPECT - (A) Manual, ROIs com dimensões padronizadas - (B) método Twobox e (C) método Threebox; e baseado em imagens estruturais (D) MRI e (E) CT. A acurácia de cada método aplicado foi avaliada através do coeficiente de correlação de concordância (CCC), sua precisão utilizando o coeficiente de Pearson e modelos regressão linear, assim como a reprodutibilidade pode ser investigada através de análises de variabilidade intra- e interobservadores. RESULTADOS: Tanto para as cavidades avaliadas de forma individual (Caudado e Putâmen), quanto para o corpo estriado como um todo, todos os métodos aplicados apresentaram um aumento no CCC dos índices quantificados diante de uma diminuição dos valores nominais de preenchimento. Os métodos D e E apresentaram os máximos valores de CCC na avaliação do núcleo caudado _ 0,89 baixo MRI CA CCC ? e _ 0,84 baixo CT CA CCC ? ) e putâmen ( _ 0,86 baixo MRI PU CCC ? e _ 0,82 baixo CT PU CCC ? ). Entretanto, na avaliação do corpo estriado, o método B apresentou a máxima acurácia dentre os cinco aplicados ( _ 0,95 baixo TWOBOX ST CCC ? ). A significante correlação entre os métodos foi evidenciada por um elevado coeficiente de correlação (r > 0.8). Na avaliação da reprodutibilidade intra e interobservadores uma grande variabilidade foi observada na aplicação do método A, principalmente quando aplicada na semiquantificação de baixas concentrações de atividade. Conclusão: Os cinco métodos semiquantitativos de SPECT do corpo estriado, demonstraram ser eficientes na realização de leituras proporcionais dos índices de BPI mesmo quando aplicados a imagens de diferentes concentrações de atividade. Porém, diante de investigações que necessitem de um processo de quantificação mais acurado e visando avaliar putâmen e núcleo caudado de forma isolada, os métodos estruturais (MRI e CT), demonstraram uma crescente eficiência em representar acurados parâmetros semiquantitativos diante da diminuição dos índices nominais de preenchimento. Na investigação de todo o corpo estriado e carente de qualquer informação estrutural, o método TwoBox passa a ser recomendado devido sua melhor performance diante todos os métodos avaliados. / AIM: The molecular image of dopamine transporters (DAT) gives differential information in research of neurodegenerative diseases, such as Parkinson\'s, when properly approached quantitatively. Yet, each method used in clinical routine may give, or not, different results when the quantifications are applied in images of several activity levels. Hence, this study assessed the accuracy, precision and reproducibility of striatum SPECT images semi-quantification methods, based in ROIs. METHODOLOGY: Twenty-three SPECT images were acquisitions of anthropomorphic striatal phantom filled with different activity concentrations of 99mTc. For each acquisition performed, the specific chambers (caudate and putamen chambers) to large chamber (simulating nonspecific background activity) was filled with solutions activity of different specific to nonspecific ratios (10, 8, 6, 4 and 2 to 1). The images were reconstructed by iterative algorithm, corrected to attenuation effects and the extracted values were analyzed by the specific binding ratio (SBR). Five semi-quantification methods for striatum SPECT, using ROIs was assessment: (A) draw freehand ROIs on SPECT image (manual); standard size ROIs: (B) TwoBox and (C) ThreeBox Methods and VOIs using structural images: (D) MRI and (E) CT. Accuracy of methods applied was assessed by concordance correlation coefficient (CCC) and precision by Pearson\'s coefficient and linear regression. RESUlTS: The SBR quantified both to individual specific chambers and striatal chamber analyzed to all methods applied resulted in a CCC increase with decrease of the nominal values used. For lower SBR values, the D and E methods evidenced the maximum values of CCC in assessment of caudate (CCCMRI_CA = 0.89 e CCCCT_CA = 0.84) and putamen (CCCMRI_PU = 0.86 e CCCCT_PU = 0.82). However, striatal assessments the B method highlights a maximum accuracy between all methods applied (CCCTWOBOX_ST = 0.95), for low values of SBR. A high Pearson\'s coefficient was found in the correlation between the all methods, report thereby a good precision between them (r > 0.8). The high ICC and variability values, showed a high reprodutibility intra- and interobserver for B, C and D methods, white the A and E methods presented a high variability between the raters. CONCLUSION: The five semi-quantification methods of striatum SPECT reported a high precision even when applied in images with activity solutions different. Therefore, to research much accurate and need to assessment just caudate or putamen individually the structural methods - MRI and CT - demonstrated progressive improvement in its quantification to reduction nominal fill index. To assessment striatal chamber and in the absence of structural information, the TwoBox method is advisable due to its excellent agreement with all nominal values when compared to the various semi-quantitative methods investigated. Keywords:

HMPV was first reported in Australia by Nissen et al in 2002 from a group of 200 nasopharyngeal aspirate (NPA) specimens collected throughout 2001 from children presenting to the Royal Children’s Hospital, Brisbane. These specimens, previously negative for all common viral pathogens, were screened for hMPV by a polymerase chain reaction (PCR) assay based on known sequences. Molecular diagnostic assays including conventional reverse transcriptase PCR assay (RT-PCR) and real-time RT-PCR assays were subsequently developed, and molecular characterisation studies in our laboratory identified four genetic groups of hMPV. At the start of this project, little information were available regarding the virological characteristics of hMPV such as the isolation and replication kinetics of the virus in eukaryotic cells, molecular assays capable of detecting all virus subtypes, quantitation of viral load, genotyping and molecular epidemiology, correlation between virus subtypes and disease severity, and clinical spectrum of the infection. This project was designed to elucidate the virological features of hMPV that had not been explained by earlier studies on this virus. The project was limited to retrospective studies utilising the sera and nucleic acids obtained from positive subjects presenting to our hospital. The project provided relevant data in these areas, which helped in the early detection of infection and treatment, and also provided information for future research on antibody profiles and vaccine development. The study examined specific areas related to clinical and virological characteristics of hMPV with the aim of applying the results in patient management. During the project, five areas of hMPV research were undertaken, addressing each through detailed studies. An outline of the project aims and the conclusions derived from those experimental chapters is described below: 1. Isolation of the virus from clinical specimens obtained from infected subjects An optimised tissue culture protocol was successfully developed for isolating hMPV from positive nasopharyngeal aspirates, using LLC-MK2 cell lines. Viral stocks were prepared and maintained at stable conditions for future experiments. The demonstration of virus infection in the eukaryotic cells and titration of the infectious virions were performed using immunological assays developed and optimised in our laboratory, during the course of this study. 2. The complete genome sequence of an Australian hMPV isolate In this study, we described the ‘13,333 base pair’ complete genome sequence of the Queensland hMPV type-A strain, designated as AUS-001. Phylogenetic analyses of individual genes were used to generate ‘topological trees’ for systematic comparison of our local hMPV strain to that of international sequences. 3. A quantitative PCR assay (q.PCR) for hMPV A quantitative real-time reverse transcription PCR assay (qrt.RT-PCR) was developed for the simultaneous detection and quantification of hMPV in clinical samples. Serial dilutions of a synthetic RNA control were amplified after determining the absolute RNA copy numbers, and a standard curve was derived based on the cycle thresholds (Ct) values of the respective dilutions. Quantification of the hMPV RNA in clinical specimens was performed by extrapolating this data with Ct values of specimen dilutions obtained from the real-time assay. The dynamic range of the assay for hMPV genotypes A and B was determined. Validation of the inter- and intra- assay variations was completed using negative and positive controls along with a second assay targeting a different gene. 4. Determine the molecular epidemiology of hMPV genotypes This component of the project was designed to determine the molecular epidemiology of Queensland hMPV strains, using a selected ‘specimen population of hMPV positives’ representing the period 2001 to 2004. An RT-PCR assay based on P gene regions of hMPV was developed for the molecular typing of the above panel. Analyses of nucleotide and predicted amino acid sequences confirmed the heterogeneity of hMPV strains. In our study group, two genotypes (A and B) further classified into four subtypes (A1, A2, B1 and B2), were found to co-circulate during this period. General epidemiological features of the hMPV infections including seasonality, co-infections, incidence and prevalence in different age groups and in general population were described. 5. Clinical characteristics of hMPV infections The aim of this analysis was to illustrate the clinical spectrum of hMPV infections in a Queensland study population. We described the hMPV incidence pattern in different age groups and investigated the clinical severity scores of hMPV genotypes based on reported clinical features. We also undertook to identify any correlations between disease severity and other factors, including genotype, co-infections and viral load. Summary On completion, this PhD study provided valuable data on the isolation, molecular detection, epidemiological pattern and clinical severity of hMPV infections in Queensland. Overall hMPV was determined to be a serious respiratory pathogen in Queensland children. Data from this thesis will contribute to improved patient management and reduce the burden of hMPV-related disease in Queensland. These studies also formed the basis of further research involving respiratory viral pathogens in our laboratory and nationally.

HMPV was first reported in Australia by Nissen et al in 2002 from a group of 200 nasopharyngeal aspirate (NPA) specimens collected throughout 2001 from children presenting to the Royal Children’s Hospital, Brisbane. These specimens, previously negative for all common viral pathogens, were screened for hMPV by a polymerase chain reaction (PCR) assay based on known sequences. Molecular diagnostic assays including conventional reverse transcriptase PCR assay (RT-PCR) and real-time RT-PCR assays were subsequently developed, and molecular characterisation studies in our laboratory identified four genetic groups of hMPV. At the start of this project, little information were available regarding the virological characteristics of hMPV such as the isolation and replication kinetics of the virus in eukaryotic cells, molecular assays capable of detecting all virus subtypes, quantitation of viral load, genotyping and molecular epidemiology, correlation between virus subtypes and disease severity, and clinical spectrum of the infection. This project was designed to elucidate the virological features of hMPV that had not been explained by earlier studies on this virus. The project was limited to retrospective studies utilising the sera and nucleic acids obtained from positive subjects presenting to our hospital. The project provided relevant data in these areas, which helped in the early detection of infection and treatment, and also provided information for future research on antibody profiles and vaccine development. The study examined specific areas related to clinical and virological characteristics of hMPV with the aim of applying the results in patient management. During the project, five areas of hMPV research were undertaken, addressing each through detailed studies. An outline of the project aims and the conclusions derived from those experimental chapters is described below: 1. Isolation of the virus from clinical specimens obtained from infected subjects An optimised tissue culture protocol was successfully developed for isolating hMPV from positive nasopharyngeal aspirates, using LLC-MK2 cell lines. Viral stocks were prepared and maintained at stable conditions for future experiments. The demonstration of virus infection in the eukaryotic cells and titration of the infectious virions were performed using immunological assays developed and optimised in our laboratory, during the course of this study. 2. The complete genome sequence of an Australian hMPV isolate In this study, we described the ‘13,333 base pair’ complete genome sequence of the Queensland hMPV type-A strain, designated as AUS-001. Phylogenetic analyses of individual genes were used to generate ‘topological trees’ for systematic comparison of our local hMPV strain to that of international sequences. 3. A quantitative PCR assay (q.PCR) for hMPV A quantitative real-time reverse transcription PCR assay (qrt.RT-PCR) was developed for the simultaneous detection and quantification of hMPV in clinical samples. Serial dilutions of a synthetic RNA control were amplified after determining the absolute RNA copy numbers, and a standard curve was derived based on the cycle thresholds (Ct) values of the respective dilutions. Quantification of the hMPV RNA in clinical specimens was performed by extrapolating this data with Ct values of specimen dilutions obtained from the real-time assay. The dynamic range of the assay for hMPV genotypes A and B was determined. Validation of the inter- and intra- assay variations was completed using negative and positive controls along with a second assay targeting a different gene. 4. Determine the molecular epidemiology of hMPV genotypes This component of the project was designed to determine the molecular epidemiology of Queensland hMPV strains, using a selected ‘specimen population of hMPV positives’ representing the period 2001 to 2004. An RT-PCR assay based on P gene regions of hMPV was developed for the molecular typing of the above panel. Analyses of nucleotide and predicted amino acid sequences confirmed the heterogeneity of hMPV strains. In our study group, two genotypes (A and B) further classified into four subtypes (A1, A2, B1 and B2), were found to co-circulate during this period. General epidemiological features of the hMPV infections including seasonality, co-infections, incidence and prevalence in different age groups and in general population were described. 5. Clinical characteristics of hMPV infections The aim of this analysis was to illustrate the clinical spectrum of hMPV infections in a Queensland study population. We described the hMPV incidence pattern in different age groups and investigated the clinical severity scores of hMPV genotypes based on reported clinical features. We also undertook to identify any correlations between disease severity and other factors, including genotype, co-infections and viral load. Summary On completion, this PhD study provided valuable data on the isolation, molecular detection, epidemiological pattern and clinical severity of hMPV infections in Queensland. Overall hMPV was determined to be a serious respiratory pathogen in Queensland children. Data from this thesis will contribute to improved patient management and reduce the burden of hMPV-related disease in Queensland. These studies also formed the basis of further research involving respiratory viral pathogens in our laboratory and nationally.

Im Rahmen der vorliegenden Dissertationsschrift „Semi-quantitative röntgentomographische Untersuchungen zur Biodistribution von magnetischen Nanopartikeln in biologischem Gewebe“ wurden tomographische Untersuchungen an biologischen Objekten durchgeführt. Bei diesen Objekten handelt es sich um Gewebeproben nach minimal-invasiven Krebstherapien wie zum Beispiel magnetischem Drug Targeting und magnetischer Wärmebehandlung. Der Erfolg dieser Therapien ist sowohl abhängig von der korrekten Verteilung der magnetischen Nanopartikel als auch von der Tatsache, dass diese in der Zielregion in einer ausreichenden Menge vorhanden sind. Das Vorliegen dieser beiden Voraussetzungen ist in der vorliegenden Arbeit untersucht worden. Dabei lag der Schwerpunkt der Arbeit auf der Quantifizierung von magnetischem Material in unterschiedlichen biologischen Gewebeproben mittels Röntgenmikrocomputertomographie (XµCT). Für diesen Zweck wurde ein Kalibrationssystem mit speziellen Phantomen entwickelt, mit dessen Hilfe eine Nanopartikelkonzentration einem Grauwert voxelweise zugewiesen werden kann. Mit Hilfe der Kalibration kann der Nanopartikelgehalt sowohl in monochromatischen als auch in polychromatischen tomographischen Daten im Vergleich zu magnetorelaxometrischen Ergebnissen mit wenigen Prozent Abweichung ermittelt werden. Trotz Polychromasie und damit einhergehenden Artefakten können 3-dimensionale röntgentomographische Datensätze mit einer geringfügigen Konzentrationsabweichung im Vergleich zur quantitativen Messmethode Magnetorelaxometrie semi-quantitativ ausgewertet werden. / The success of the minimal invasive cancer therapies, called magnetic drug targeting and magnetic heating treatment, depends strongly on the correct distribution of the magnetic nanoparticles on one side. On the other side it depends on the fact that a sufficient amount of magnetic nanoparticles carrying drugs is accumulated in the target region. To study whether these two requirements are fulfilled motivates this PhD thesis „Semi-quantitative X-ray-tomography examinations of biodistribution of magnetic nanoparticles in biological tissues“. The analysis of the distribution of the magnetic nanoparticles in tumours and other tissue examples is realized by means of X-ray-micro computer tomography (XμCT). The work focuses on the quantification of the magnetic nanoparticles in different biological tissue samples by means of XµCT. A calibration of the tomographic devices with adequate phantoms, developed in the frame of this work, opens now the possibility to analyze tomographic data in a semi-quantitative manner. Thus, the nanoparticle concentration can be allocated voxel-wise to the grey values of the three-dimensional tomographic data. With the help of calibration of the tomography equipments used, polychromatic as well as monochromatic three-dimensional representations of objects can be analyzed with regard to the biodistribution of magnetic nanoparticles as well as with regard to their quantity. The semi-quantitative results have been compared with results obtained with a quantitative measurement method magnetorelaxometry (MRX). Thereby a good agreement of the semi-quantitative and quantitative data has been figured out.

Im Rahmen der vorliegenden Dissertationsschrift „Semi-quantitative röntgentomographische Untersuchungen zur Biodistribution von magnetischen Nanopartikeln in biologischem Gewebe“ wurden tomographische Untersuchungen an biologischen Objekten durchgeführt. Bei diesen Objekten handelt es sich um Gewebeproben nach minimal-invasiven Krebstherapien wie zum Beispiel magnetischem Drug Targeting und magnetischer Wärmebehandlung. Der Erfolg dieser Therapien ist sowohl abhängig von der korrekten Verteilung der magnetischen Nanopartikel als auch von der Tatsache, dass diese in der Zielregion in einer ausreichenden Menge vorhanden sind. Das Vorliegen dieser beiden Voraussetzungen ist in der vorliegenden Arbeit untersucht worden. Dabei lag der Schwerpunkt der Arbeit auf der Quantifizierung von magnetischem Material in unterschiedlichen biologischen Gewebeproben mittels Röntgenmikrocomputertomographie (XµCT). Für diesen Zweck wurde ein Kalibrationssystem mit speziellen Phantomen entwickelt, mit dessen Hilfe eine Nanopartikelkonzentration einem Grauwert voxelweise zugewiesen werden kann. Mit Hilfe der Kalibration kann der Nanopartikelgehalt sowohl in monochromatischen als auch in polychromatischen tomographischen Daten im Vergleich zu magnetorelaxometrischen Ergebnissen mit wenigen Prozent Abweichung ermittelt werden. Trotz Polychromasie und damit einhergehenden Artefakten können 3-dimensionale röntgentomographische Datensätze mit einer geringfügigen Konzentrationsabweichung im Vergleich zur quantitativen Messmethode Magnetorelaxometrie semi-quantitativ ausgewertet werden. / The success of the minimal invasive cancer therapies, called magnetic drug targeting and magnetic heating treatment, depends strongly on the correct distribution of the magnetic nanoparticles on one side. On the other side it depends on the fact that a sufficient amount of magnetic nanoparticles carrying drugs is accumulated in the target region. To study whether these two requirements are fulfilled motivates this PhD thesis „Semi-quantitative X-ray-tomography examinations of biodistribution of magnetic nanoparticles in biological tissues“. The analysis of the distribution of the magnetic nanoparticles in tumours and other tissue examples is realized by means of X-ray-micro computer tomography (XμCT). The work focuses on the quantification of the magnetic nanoparticles in different biological tissue samples by means of XµCT. A calibration of the tomographic devices with adequate phantoms, developed in the frame of this work, opens now the possibility to analyze tomographic data in a semi-quantitative manner. Thus, the nanoparticle concentration can be allocated voxel-wise to the grey values of the three-dimensional tomographic data. With the help of calibration of the tomography equipments used, polychromatic as well as monochromatic three-dimensional representations of objects can be analyzed with regard to the biodistribution of magnetic nanoparticles as well as with regard to their quantity. The semi-quantitative results have been compared with results obtained with a quantitative measurement method magnetorelaxometry (MRX). Thereby a good agreement of the semi-quantitative and quantitative data has been figured out.