Periprosthetic joint infections by antibiotic-resistant biofilm-forming pathogenic bacteria such as Staphy-lococcus aureus are a growing concern in the field of arthroplasty. They are difficult to treat and can lead to implant revision surgery, health complications, and in some cases death. An established method in clinical practice for delivering antibiotics directly to the site of surgery is the use of antibiotic-loaded polymethyl methacrylate (PMMA), a synthetic polymer used to integrate joint implants into bone tissue. With rising rates of antibiotic resistance, researchers are looking for alternative treatments for bacterial infections and one of the possible candidates is targeted alpha therapy (TAT). Ra-223 is one such alpha emitter which is already being used in a clinical setting under the name Xofigo®to treat cancer. With the ability of PMMA to be loaded with pharmaceuticals, it may be worthwhile to investigate whether radioistopes such as Ra-223 can also be loaded and released from the polymer. In this thesis, the potential use of PMMA as a radioisotope delivery vehicle is investigated, as well as the bactericidal capacity of Ra-223 against S. aureus are investigated.
To achieve this, PMMA was loaded separately with two different radioisotopes, Ga-68 and Ra-223. The loading was done with and without the presence of a chelator. The release of the isotopes from PMMA was measured over time. Growth of S. aureus cultures was measured under different activities of Ra-223 and growth curves were constructed. The uptake of Ra-223 by the bacteria was also measured.
A minimum of 50% Ga-68 was found to be released when freely added to PMMA. This was due to the insolubility of the Ga-68 eluate in PMMA, causing the isotope to be concentrated in a single spot. However, the addition of a chelator significantly dampened the release to maximum of 3%, since Ga-68 was homogeneously dispersed throughout the PMMA volume. Ra-223 was shown to have a similar release when added freely to PMMA (47%), but the chelator used was shown not to extract any Ra-223 to the PMMA and therefore no release was observed. There was no measurable bactericidal effect of Ra-223 on S. aureus for the activities used in the experiments. It was found that 8±5% of the total amount of Ra-223 was taken up by the bacteria after 18 h of incubation.
Although PMMA seems to exhibit some radioisotope release, further experiments need to be carried out to determine if these amounts can evoke a bactericidal effect. The percentage of Ra-223 taken up by S. aureus shows that the isotope has some promise as a potential bactericide against it, but experiments with higher activities need to be carried out. Furthermore, future experiments are needed to determine the internalization of Ra-223 by S. aureus.

The radionuclide technetium-99m (99𝑚Tc) is utilized in 80-85% of in-vivo nuclear medicine diagnostics due to its ideal physical and chemical properties, including a short half-life, gamma emission suitable for imaging, and versatile chemistry. Its production relies on molybdenum-99 (99Mo), traditionally generated through uranium fission. However, the transition to low-enriched uranium (LEU) targets and growing demand for 99𝑚Tc have driven the search for alternative production methods and materials. This study investigates the potential of molybdenum silicide (MoSi2) materials as targets for neutron-activated 99Mo production and as generators for 99𝑚Tc extraction. Three synthesis methods were explored to produce nanoscale molybdenum silicides. A sol-gel carbothermic reduction method failed to produce MoSi2, yielding elemental molybdenum, molybdenum dioxide, and molybdenum carbide due to oxygen contamination. The sol-gel preoxidation method successfully coated commercial MoSi2 with an amorphous silica layer, enhancing the material’s stability. The magnesiothermic reduction method successfully produced an oxide mixture intermediate (SiO2/MoO3) with nanosphere structures, initially containing 0.57 wt% molybdenum. The molybdenum content was later increased to 23.96 wt%. However, synthesis of the Si/MoSi2 nanocomposites from this intermediate was not completed due to time constraints. The chemical stability, extraction and retention behavior of commercial and silica-coated MoSi2 were evaluated in MilliQ and methyl ethyl ketone (MEK). The silica coating reduced molybdenum leaching and exhibited selective 99𝑚Tc extraction. Retention studies highlighted the significant role of solvent interactions in governing radionuclide adsorption. In MEK, the silica-coated material exhibited lower 99𝑚Tc retention, likely due to reduced adsorption sites caused by solvent interactions with silanol groups, while 99Mo retention could not be evaluated due to insufficient extraction data. The results demonstrate the potential of silica-coated MoSi2 in 99Mo/99𝑚Tc generator applications. However, further work is needed to optimize synthesis, increase surface area and evaluate long-term performance under irradiation. This could pave the way for sustainable and efficient isotope production systems.

¹⁶¹Tb is considered a promising alternative to ¹⁷⁷Lu in the treatment of neuroendocrine tumors and prostate cancer. It is produced via neutron irradiation of ¹⁶⁰Gd targets and its subsequent separation from said targets. Current separation methods have limitations so a fast removal method of the Gd bulk is desired. Such a method is developed in this research using solvent extraction techniques. Three extractants were investigated, the one with the highest potential, DEHPA, was used to optimize the extraction. This yielded a Tb extraction efficiency of 98.6 ± 0.2 % and a Gd extraction efficiency of 85.7 ± 5.5 % followed by a Tb back-extraction efficiency of 98.2 ± 0.1 % and a Gd back-extraction efficiency of more than 98.2 ± 0.1 %. The Tb/Gd separation was increased by adding the reverse size selective chelator MACROPA to the aqueous phase to preferentially complex Gd in the aqueous phase. This yielded a Tb and Gd extraction efficiency of 95.0 ± 0.2 % and 53.1 ± 3.0 % respectively. The ratio between total EEs of Tb and Gd after three subsequent extractions was approximately 10 demonstrating the potential of using sequential extractions to remove a bulk of Gd from Tb. The procedure of doing consecutive extractions must however be further optimized as nearly 80% of Tb was not extracted. Finally, it was shown that the resulting solution after bulk Gd removal can still be further purified using an ion exchange column. In future research, it is highly advised to investigate the recycling of Gd and MACROPA from the aqueous phase after extraction to allow for further irradiation of the Gd and re-usability of the MACROPA.

Technetium-99m (^99mTc) is a critical isotope in nuclear medicine, used for diagnostic imaging. It is conventionally produced in a aluminum oxide ⁹⁹Mo/^99mTc generator that runs on molybdenum-99 (⁹⁹Mo) produced by fission of uranium-235. This fission-based production method faces several challenges. To address these challenges, alternative production pathways are being explored. Neutron irradiation of enriched ⁹⁸Mo nanomaterials and proton bombardement of enriched ¹⁰⁰Mo nanomaterials are two of the possible options. Within this research, the pathway of ⁹⁸Mo neutron capture will be the focus.
Developing a novel circular low specific activity 99Mo/99mTc generator that can run on these materials requires research to be done into the potential materials. The materials must meet two qualifying conditions: they should have a high surface-to-volume ratio, and show high radionuclide extraction potentials. This is an exploratory study to determine if molybdenum disulfides can be synthesized to meet those conditions.
Multiple synthesis methods of MoS₂ nanostructures were explored, and insights were given on their morphological and compositional characteristics. Of the six synthesized materials, four were MoS₂ nanospheres, one was MoS₂ microcubes and one was unable to be characterized
due to unsuccessful separation of the product. Two of the products were further evaluated on their stability and surface area. Stability tests in milliQ were done under two conditions: five consecutive cycle washes and five time-based washing cycles. Both materials exhibited lower Mo breakthrough during the consecutive washes than during the time-based wash cycles. The most compelling results were the downward trend that the Mo breakthrough data shows for the consecutive washes and the high breakthrough percentage in the 24 h soak for one of the samples (namely, 1.2 ± 0.28%) . Furthermore, the same two materials were tested on irradiation performance. Radionuclide extractions were made in milliQ, and extraction yields were calculated for ⁹⁹Mo.

Calcium is the most abundant mineral in the human body and is essential for building and maintaining bones and teeth. Only 20-30% of the calcium in milk can be absorbed by the human body. 90% of the insoluble calcium in milk is located in the casein micelles, and 40% of this calcium is hard to exchange.
It is important to understand how this non-exchangeable calcium behaves and whether there are ways of making it exchangeable.
In this study, the hard-to-exchange (HTE) calcium in the casein micelles of bovine skimmed milk was studied. In order to investigate this, a protocol for the preparation of artificial casein micelles was established. The hydrodynamic radius and the hydration of the casein micelles were measured to see if the artificial casein micelles could be compared to the casein micelles from bovine skimmed milk. Subsequently, 45Ca was used to track the exchange of calcium in the three different fractions of milk and artificial casein micelles: casein micelles, serum proteins, and soluble phase. (Ultra)centrifugation was used to separate the fractions.
Characterisation of bovine skimmed milk and artificial casein micelles was carried out first. The hydrodynamic radius of the casein micelles in both types of milk was determined and it was concluded that the hydrodynamic radius of both types of milk was comparable to each other. Furthermore, the hydration of casein micelles was investigated. A difference was measured between the hydration of both casein micelles. This can be explained by a small deviation in casein and fat content between the two types of milk.
In order to draw conclusions about the suitability of using artificial casein micelles to model casein micelles naturally present in milk, the protocol needs to be adapted by adjusting the casein content and removing the fat from both types of casein micelles. It is also necessary to investigate the mineral content of both types of milk.
It was found that almost half (48.8 ± 0.6%) of the 45Ca added to bovine skimmed milk was located in the supernatant, while the remaining 54.2 ± 0.6% was distributed within the casein micelles. When this distribution is compared to that of artificial casein micelles, it can be seen that the %45Ca in the artificial casein micelles is much lower than in the bovine skimmed milk casein micelles. This is because of the fact that artificial casein micelles contain a lower content of casein aggregates cross-linked with colloidal calcium phosphate (CCP) in comparison with bovine skimmed casein micelles.
When 45Ca was added after the preparation of artificial casein micelles, the HTE calcium was found to be 54.5 ± 2.6%. However, when the 45Ca was added during the preparation of artificial casein micelles and measured after 0 hours, the HTE calcium was 63.1 ± 2.0% and after 24 hours it was determined to be 59.6 ± 3.4%. These values were not in agreement with the values from Zhang et al. [1].
Overall, this project contributed to a better understanding of the hard-to-exchange calcium in milk using artificial casein micelles and 45Ca. It shows that further research needs to be carried out to determine whether artificial milk can be used as a model for bovine skimmed milk and to determine the HTE calcium in artificial casein micelles.

Holmium-166 is a promising radionuclide for therapeutic and imaging applications due to its advantageous decay characteristics. However, these applications require or would benefit from a higher specific activity of ¹⁶⁶Ho than that obtained via a ¹⁶⁵Ho(n,γ)¹⁶⁶Ho reaction by irradiating a pure ¹⁶⁵Ho target. The specific activity is limited, because only a minor fraction of the ¹⁶⁵Ho target nuclides is converted into ¹⁶⁶Ho during irradiation and these isotopes are inseparable using conventional chemical methods, since they are of the same element. The Szilard-Chalmers effect facilitates this separation by changing the chemical state of the produced radionuclide due to the recoil induced by neutron absorption. Nevertheless, currently applied target materials, mainly ligands, are unsuitable for commercial scale production with sufficient yield and specific activity, because of: radiolysis, isotopic interchange and recombination. It is proposed that these processes can be significantly reduced by exploiting zeolites, which are materials with interconnected cavities, to bind ¹⁶⁵Ho target nuclides in the closed cages prior to irradiation. The concept behind is, that upon recoil the ¹⁶⁶Ho nuclides relocate to the open cages, from which they are extracted after irradiation, while the ¹⁶⁵Ho target nuclides remain locked in the closed cages. This results in an increased specific activity. Therefore, the aim of this thesis is to examine the increase in the specific activity of ¹⁶⁶Ho produced via a (n,γ) reaction by applying the Szilard-Chalmers effect using zeolite A.

A procedure to achieve the optimal loading of holmium into the open cages (18.3 wt% Ho) and closed cages (93.3% of total holmium) of zeolite A was investigated, as well as the efficiency of its extraction from the open cages (between 39 and 55%). The obtained specific activity and yield were analysed upon irradiation of these zeolite A samples. Irradiating zeolite A with ¹⁶⁵Ho exclusively in the open cages resulted in only a slight increase of the specific activity (maximal 3.3 GBq/g), but a relatively good yield (maximal 53%). In contrast, irradiation of zeolite A with ¹⁶⁵Ho loaded in both the closed and the open cages, resulted in a considerably lower yield (maximal 14.4%), but a substantially increased specific activity (maximal 7.3 GBq/g), which is a factor 5.2 higher than without the Szilard-Chalmers effect. 
Nevertheless, further improvement should be considered as a higher specific activity is key to successful radionuclide therapy. This could potentially be achieved by increasing the extraction efficiency by exploring other types of zeolites, in search of more suitable functional characteristics.