Towards Alpha Dosimetry with Laser Ionized and Mass Separated 225Ac: Setup Development and Source Characterization

Metastatic cancers are responsible for ∼90% of cancer-related deaths. Yet when patients are faced with metastasis, they often have little choice but to resort to chemotherapy. A possible alternative can be found in targeted therapies. In these, radionuclides are chelated to vector molecules, designed to bind with cancer cells. Since 2013, Targeted Alpha Therapy (TAT) has become a clinical reality with the approval of the first alphaemitting radiopharmaceutical, Xofigo$^{TM}$. Thanks to the alpha-particle’s short path length (<100μm) and high energy (4-10 MeV), TAT is particularly appropriate for targeting distributed cancers. A promising radionuclide for TAT, $^{225}$Ac, is currently under clinical investigation yet supply issues persist. Furthermore, the radiobiological effects of alpha particles are still not fully understood. To respond to supply shortages, a new, accelerator-based production route for $^{225}$Ac is being explored. In this method, high energy (>70 MeV) protons are used to induce spallation reactions on solid uranium or thorium-based targets. Afterwards, produced isotopes can be extracted and purified via laser ionization and mass separation. A sample from CERN-MEDICIS which was produced using this technique was characterized. End Of Collection (EOC) activity was obtained via γ-γ coincidence measurements and compared to in-target yields. Furthermore, suitability for medical applications was investigated by determining the suppression factor of $^{227}$Ac via alpha spectroscopy. An EOC activity of 201 kBq was achieved for a target of 4.52 MBq, resulting in a collection efficiency of 4.44%. The activity of $^{227}$Ac on the sample was estimated to be 0.080 Bq or 5.8 × 10$^{−5}$ % of the $^{225}$Ac activity based on preliminary analysis. One of the main reasons that microbiological effects of alpha particles are poorly understood is the lack of precise and accessible research methods. To this end, DIRAC, a setup for the irradiation of cells with alpha particles was developed. Exploiting the properties of cells suspended in a hydrogel, it can irradiate cells with access to neither radiopharmaceuticals nor specialized equipment. Simulations were performed in Geant4 to investigate the feasibility of the technique and a protocol for cell irradiation was developed. Proof of concept was then achieved over an experimental campaign where HeLa cancer cells were irradiated by sources of $^{225}$Ac and $^{241}$Am. Life/death assays using fluorescence microscopy confirmed the response of cancer cells to radiation. To the author’s knowledge, DIRAC is the first-ever setup to use this technique exploiting hydrogels in conjunction with alpha radiation. Its success can provide useful radiobiological data for the development of TAT. Further investigation and development of this technique is thus warranted.