Heating properties of holmium doped nanoparticles

For image guided thermo-brachytherapy

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Abstract

Because diagnostics have improved tremendously, nowadays breast cancer is more frequently detected at an early stage. Long-term prognosis is excellent and therefore the new treatment should focus on minimizing long-term side effects and treatment burden. This research proposes cancer treatment using nanoparticles (NPs) for a combination of heat therapy and brachytherapy. For the NP design, superparamagnetic iron-oxide nanoparticles (SPIONs) will be used. Because of their biocompatibility and good magnetic properties, they are suitable candidates for heating using an alternating magnetic field. To make the NPs applicable for brachytherapy, the NPs are doped with holmium (Ho), a lanthanide with high magnetic moment and radioisotope Ho-166. Furthermore, SPIONs and Ho change the relaxivity of water
protons and therefore they can be used as contrast agents for magnetic resonance imaging. This makes it possible to image the NPs during the treatment and enables thermal planning and dose-rate calculations delivered to the cancer tissue to be performed. The incorporation of Ho inside the iron-oxide structure is expected to change the magnetic properties of the NPs. The success of using Ho as contrast agent and for brachytherapy purposes have been proven in several researches. However, the influence of Ho on the heating performance of these SPIONs is unknown. This research will characterize the magnetic properties of undoped and Ho-doped SPIONs and compare them, in order to examine the heating possibilities of Ho-doped NPs. For the synthesis of the NPs a spark discharge generator was used. Spark ablation is a synthesis
method able to yield narrow size distribution of different metallic particles and alloys. However, since spark ablation is relatively new, the synthetic methodology itself had to be developed. Therefore, this research was divided into two parts: 1) the synthesis of NPs using spark ablation and 2) the characterization of Ho-doped iron NPs and the comparison with undoped SPIONs. Since the first part focused on the spark ablation synthesis, the influence of the generator settings on the primary particle size was investigated using DLS and TEM. The VS-Particle generator was able to produce 4 nm Fe-Fe and Ho-Fe NPs, a size that is smaller than expected. The generator settings did not influence the primary particle size and therefore, the settings of the generator were chosen to maximize the yield. The initial set-up had low yield and therefore, the influence of micro-bubbler, electrode configuration and bubbling column were examined and changed to improve the yield. A bronze sintered filter with pore size 0.4-20 ��, solid iron electrodes and 60 mL bubbling column volume appeared to be the most optimal. During the second part of this research, 4 nm Ho-doped iron oxide NPs and un-doped iron oxides were produced. They were characterized using TEM, DLS, XRD, ICP, SEM-EDX, Mössbauer spectroscopy, SQUID and NMR. As a result of low concentrations obtained, no good qualification of the produced particles could be obtained. All particles showed superparamagnetic behavior and influenced the relaxivity times of water protons. To what extend the relaxivity was changed upon doping remains unfortunately unclear, because the composition of the NPs is unknown. It can be concluded that the used set-up was not able to produce reproducible NPs and therefore no reliable characterization could be done on the Ho doped particles. Future research should focus on a more controllable synthesis method to be able to examine the possibilities of Ho for heating purposes.