Development of a cell-irradiation protocol and $^{225}$Ac recoil-implantation generator for alpha radiobiology

Nowadays, whenever a patient is diagnosed with metastatic cancer, the survival rate following diagnosis is typically low. For example, of all patients diagnosed with metastatic breast cancer only 28% of all women (and 22% of all men) will still be alive after five years. This number drops to 7% for patients diagnosed with metastatic lung cancer [1]. However, in the last two decades, promising results have been observed in clinical trials using targeted alpha therapy (TAT) for treating metastatic cancers. In TAT, an alpha emitting radionuclide is attached to a vector that will carry the radionuclide towards the cancer cells by traveling along the circulatory and lymphatic system in the body. Even though the clinical trials look promising, TAT is nowadays not on a large scale clinically in use for cancer treatment. This is mainly due to (1) the high costs, (2) the availability and (3) the effects of the alpha-emitting sources and their recoiling daughter nuclei on (cancer) cells that are not yet fully understood. In the first part of this thesis, the focus will be on the further development of a cell-irradiation protocol that can be used to determine the radiobiological effects of the emitted alpha particles in the decay of $^{225}$Ac and subsequent daughter nuclei. The development of this protocol is the first step in a larger experimental endeavor to probe the radiobiological effects of the recoiling $^{225}$Ac daughter nuclei. The goal of this protocol is to study the impact of the alpha particles on the cancerous cells by externally irradiating a hydrogel containing HeLa cells with alpha particles. After irradiation, the cell survival can be determined using, for instance, a Resazurin assay. In this project, three shortcomings of the existing protocol developed in earlier work were identified and modified: (1) The cell sedimentation inside the hydrogels was improved, such that the embedded cells are within reach of the alpha particles, (2) the protocol was adjusted such that sample manipulations during the measurements are minimized which reduces the chance of disrupting or damaging the hydrogels and (3) the glass slides required in the sample preparation were provided with a coating to avoid gel rupture. Afterwards, with the modified protocol, two new cell-irradiation experiments were performed. In the second part of this thesis, the focus will be on the development of a recoil implantation generator that can be used for the production of isotopes for cell-irradiation experiments. Whenever an $^{225}$Ac isotope decays on an $^{225}$Ac implanted foil, the remaining daughter nucleus might recoil out of the foil as a result of conservation of momentum. The idea behind the recoil-implantation generator is to implant these recoiling $^{225}$Ac daughter nuclei on an empty aluminium disk. In this project, a setup was constructed from scratch and two measurements were performed. In the first part of each measurement, an empty aluminium disk is placed in front of an $^{225}$Ac implanted foil while in the second part the implanted disk is placed in front of a passivated implanted planar silicon (PIPS) detector to identify the collected daughter nuclei. Subsequently, an expression was derived to determine the efficiency of the recoiling process from the data obtained during both measurements.