Es wurden Goldnanopartikel (AuNP) hergestellt, die eine einheitliche Größenverteilung von 3–5 nm aufweisen. Damit kann eine Mehrfachfunktionalisierung erreicht werden, d.h. gleich mehrere tumorspezifischen Moleküle an einen AuNP gekoppelt werden können und somit eine stark erhöhte Avidität zur Tumorzelle erzielt werden kann. Diese so hergestellten AuNP wurden mit diagnostisch oder therapeutisch wirksamen Radionukliden beladen bzw. radiomarkiert. Diese so funktionalisierten und radiomarkierten AuNP reicherten sich in Tumorgewebe an mit nur geringfügiger Akkumulation in gesundem Gewebe.:1. Einleitung 1 1.1 Radioaktive Arzneimittel zur Diagnostik und Therapie in der Nuklearmedizin 1 1.2 Radioaktives Gold gegen Krebs 2 1.3 Aktueller Stand der Forschung zu Goldnanopartikeln 3 1.4 Chemische Charakterisierung von oberflächen-modifizierten AuNP 5 1.5 Zielstellung 7 2. Ergebnisse 8 2.1 Gastrin-Releasing Peptide Receptor- and Prostate-Specific Membrane Antigen-Specific Ultrasmall Gold Nanoparticles for Characterization and Diagnosis of Prostate Carcinoma via Fluorescence Imaging 8 2.2 Targeted 64Cu-labeled gold nanoparticles for dual imaging with positron emission tomography and optical imaging 20 2.3 αvβ3-Specific gold nanoparticles for fluorescence imaging of tumor angiogenesis 34 2.4 68Ga-NeoB: Preclinical results on imaging of gastrointestinal stromal tumors and determination of target receptor density in the gastrointestinal tract 65 2.5 GMP-compliant production of [68Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor 80 2.6 Ac-EAZY! Towards GMP-Compliant Module Syntheses of 225Ac-Labeled Peptides for Clinical Application 93 3. Diskussion 105 3.1 Entwicklung von klinisch anwendbaren radiomarkierten Goldnanopartikeln gegen Krebs 105 3.2 Klinische Translation von neuen diagnostischen und therapeutischen Radiopharmaka 106 4. Zusammenfassung und Ausblick 108 5. Literaturverzeichnis 110 Abkürzungsverzeichnis 115 Erklärungen und Versicherung 117 / Gold nanoparticles (AuNPs) with a uniform size distribution of 3-5 nm were produced. This allows multiple functionalization to be achieved, i.e. several tumour-specific molecules can be coupled to one AuNP at the same time and thus a greatly increased avidity to the tumour cell can be achieved. These AuNPs produced in this way were loaded or radiolabeled with diagnostically or therapeutically effective radionuclides. These functionalized and radiolabeled AuNPs accumulated in tumour tissue with only slight accumulation in healthy tissue.:1. Einleitung 1 1.1 Radioaktive Arzneimittel zur Diagnostik und Therapie in der Nuklearmedizin 1 1.2 Radioaktives Gold gegen Krebs 2 1.3 Aktueller Stand der Forschung zu Goldnanopartikeln 3 1.4 Chemische Charakterisierung von oberflächen-modifizierten AuNP 5 1.5 Zielstellung 7 2. Ergebnisse 8 2.1 Gastrin-Releasing Peptide Receptor- and Prostate-Specific Membrane Antigen-Specific Ultrasmall Gold Nanoparticles for Characterization and Diagnosis of Prostate Carcinoma via Fluorescence Imaging 8 2.2 Targeted 64Cu-labeled gold nanoparticles for dual imaging with positron emission tomography and optical imaging 20 2.3 αvβ3-Specific gold nanoparticles for fluorescence imaging of tumor angiogenesis 34 2.4 68Ga-NeoB: Preclinical results on imaging of gastrointestinal stromal tumors and determination of target receptor density in the gastrointestinal tract 65 2.5 GMP-compliant production of [68Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor 80 2.6 Ac-EAZY! Towards GMP-Compliant Module Syntheses of 225Ac-Labeled Peptides for Clinical Application 93 3. Diskussion 105 3.1 Entwicklung von klinisch anwendbaren radiomarkierten Goldnanopartikeln gegen Krebs 105 3.2 Klinische Translation von neuen diagnostischen und therapeutischen Radiopharmaka 106 4. Zusammenfassung und Ausblick 108 5. Literaturverzeichnis 110 Abkürzungsverzeichnis 115 Erklärungen und Versicherung 117

This master's thesis is an investigation and evaluation of MELCOR (a software tool for severe accident analyses regarding nuclear power plants), or more correctly of the (ASEA-Atom BWR 75) reactor model developed for version 1.8.6 of MELCOR. The main objective was to determine if MELCOR, with the reactor model in question, is able to produce satisfactory results in severe accident analyses compared to results made by MAAP, which is currently the only official software tool for this application in Sweden. The thesis work is related to the RASTEP project. This project has been carried out in several stages on behalf of SSM since 2009, with a number of specific issues explored within an NKS funded R&D project carried out 2011-2013. This investigation is related to the NKS part of the project. The purpose with the RASTEP project is to develop a method for rapid source term prediction that could aid the authorities in decision making during a severe accident in a nuclear power plant. A software tool, which also gave the project its name, i.e. RASTEP (RApid Source TErm Prediction), is therefore currently under development at Lloyd's Register Consulting. A software tool for severe accident analyses is needed to calculate the source terms which are the end result from the predictions made by RASTEP. A set of issues have been outlined in an earlier comparison between MAAP and MELCOR. The first objective was therefore to resolve these pre-discovered issues, but also to address new issues, should they occur. The existing MELCOR reactor model also had to be further developed through the inclusion of various safety systems, since these systems are required for certain types of scenarios. Subsequently, a set of scenarios was simulated to draw conclusions from the additions made to the reactor model. Most of the issues (pre-discovered as well as new ones) could be resolved. However the work also rendered a set of issues which are in need of further attention and investigation. The overall conclusion is that MELCOR is indeed a promising alternative for severe accident analyses in the Swedish work with nuclear safety. Several potential benefits from making use of MELCOR besides MAAP have been identified. In conclusion, they would be valuable assets to each other, e.g. since deviations in the results (between the two codes) would highlight possible weaknesses of the simulations. Finally it is recommended that the work on improving the MELCOR reactor model should continue. / RASTEP

Surface contamination occurs in nuclear facilities, something that is important to detect easily and efficiently. Using today’s methods to detect nuclear surface contamination may cause certain inconsistencies as the human operator is solely trusted to keep the detector at the correct distance and move it at the correct speed. This thesis project aims to address the problem of inconsistent measurements with respect to the current measurement methods. A system is designed to monitor the measurement process with regards to detector velocity and height. The system will trigger a warning when the minimum detectable activity is too high, as it would lead to inconsistent results. This system consists of a cart-detector setup with a scintillation detector and velocity measurement device(s). Software will utilize the measurement data to implement the aforementioned monitoring. The system aims to be compliant with international standards, such as the ISO 11929 and the ISO 7503 standards, and will thus make use of these standards. The result of the part-analysis for each component of the system showed a large inaccuracy regarding the Intertial Measurement Units (IMUs); hence, the robotic wheels were chosen as the main method of measuring speed for this project. The robotic wheels and the detector were shown to be sufficiently accurate for the desired measurements. The Raspberry Pi 4 model B, the on- board computer, was also shown to be performance-wise and property-wise well suited for the project. This project showed that there is a theoretical way to implement the speed of a moving detector-rig into the Minimum Detectable Activity (MDA) formula. However, the implementation investigated in this project suggests that full compatibility with ISO 7503 was not achievable. / Radioaktiv ytkontaminering förekommer i kärnkraftverk, vilket är viktigt att upptäcka snabbt och effektivt. Dagens metoder för att upptäcka radioaktiv ytkontaminering kan lida av viss osäkerhet eftersom man förlitar sig helt på att operatören kan manövrera detektorn på rätt höjd och hastighet. Detta examensarbete behandlar en lösning till det ovan nämnda problemet. Ett ”proof-of-concept”-system som kan övervaka mätprocessen designas. Genom att mäta hastighet och känna till höjden över marken kan en varning meddelas användaren när den minsta detekterbara aktiviteten (MDA) når ett tröskelvärde. Det färdiga systemet är en plattform på hjul med en scintillator- detektor monterad tillsammans med en eller flesta hastighetsmätningsenheter. Systemet bör vara kompatibelt med internationella standarder, till exempel ISO 11929 och ISO 7503. Resultaten från den utvärdering av varje individuell komponent som gjorts visade på en stor mätosäkerhet i de två utvärderade IMUerna. Detta medförde att robothjulen valdes som enda källa för hastighetsmätning. Robothjulen, samt detektorn påvisade god mätsäkerhet, väl lämpad för detta projekt. Även mikrodatorn, Raspberry Pi 4 model B, visade sig vara lämplig sett till prestanda och egenskaper. Projektet resulterade i att det är trott att det finns en lämpligt sätt att i teorin implementera hastighet som en parameter i formeln för MDA. Det är dock värt att nämna att resultaten tyder på att det i denna implementation inte var möjligt att uppnå fullständig kompabilitet ISO 7503.