PHOtonuclear Reactions (PHOR): Breakthrough Research in Radionuclides for Theranostics

• Forschungsstelle: METAS
• Projektnummer: F-5155.30105
• Projekttitel Englisch: PHOtonuclear Reactions (PHOR): Breakthrough Research in Radionuclides for Theranostics

Schlüsselwörter (Englisch)

Theranostics, therapeutic radionuclides, radiochemistry, radiopharmacy, photonuclear reactions

Kurzbeschreibung (Englisch)

Nuclear methods applied in medicine play a fundamental role in diagnosis and, increasingly, in therapy of cancer. By labelling a pharmaceutically active compound with a diagnostic radioisotope and, subsequently, with a therapeutic one, patients can be diagnosed and treated individually, manifesting the concept of personalized medicine and “theranostics”. To reach this goal, new radionuclides with optimum decay characteristics and chemical properties are essential. Their availability is presently very limited and a stable and sustainable supply in quantity and quality suitable for medical applications represents a major scientific challenge. To overcome this limitation several breakthroughs have to be accomplished. Facilities to produce such radionuclides require large scale scientific infrastructures and are extremely limited. The applicants propose research to lay the scientific foundation for a novel, almost unexplored method to make these radionuclides available for future theranostic applications. By using a high-power electron accelerator, sufficiently energetic and intense gamma-rays can be generated to induce photonuclear reactions. While such accelerators are commercially available or under development, converter targets, irradiation set-ups and subsequent chemical separations have yet to be developed. To reach this goal, a multidisciplinary approach encompassing physics, radiochemistry, and radiopharmacy is mandatory. An interdisciplinary nucleus of competence active in this field is already established in Bern, with the university of Bern and the Federal Institute of Metrology (METAS). Furthermore, nuclear medicine will be significantly strengthened at the Bern university hospital (Inselspital).

In the project we focus on the theranostic radionuclide pairs ^43,44Sc/⁴⁷Sc, ⁶⁴Cu/⁶⁷Cu and on the production of the alpha-particle emitter ²²⁵Ac, for which recently striking results in cancer therapy were obtained. At present the availability of these radioisotopes for clinical studies is almost non-existent. On the basis of already existing infrastructures constituted by the 22 MeV 20 µA electron microtron at the Federal Institute of Metrology (METAS) in Bern and by the cyclotron laboratory at the Bern University Hospital, new routes towards theranostics using photonuclear reactions to produce therapeutic radionuclides (⁴⁷Sc, ⁶⁷Cu, ²²⁵Ac), together with proton induced reactions for the PET diagnostic partners (^43,44Sc, ⁶⁴Cu) will be investigated.

Projektziele (Englisch)

The objectives are to:

1. enhance and optimize the production of the PET radionuclides by developing irradiation methods with compact solid target stations for medical cyclotrons;
2. improve nuclear data by measuring the cross section of the concerned photonuclear reactions;
3. establish a test facility for the production of therapeutic radionuclides at METAS;
4. study, simulate, design and test a prototype for a high-power target station for a future high-power electron linear accelerator;
5. develop the radiochemistry, separation, target material recovery and synthesis methods for theranostic labelled biomolecules.

Abstract (Englisch)

Subproject A: The aim here was to measure the cross-sections of photonuclear reactions. An activation method was selected for this purpose. Here, targets are irradiated at several beam energies. The yield of the radionuclide produced by the photonuclear reaction is then determined using gamma spectroscopy. If the photon flux at the target is also known, an effective cross-section can be calculated from the measurement data. In order to implement this method at METAS, the measurement of the beam current was extended so that the total charge of each individual pulse is recorded. The total charge can then be determined by summing up. The method was calibrated with a Faraday cup independently of the activation. Detailed Monte Carlo simulations of the setup were also carried out. The quality of these simulations was verified by dosimetric measurements according to metrological standards. With the help of these extensions, the photonuclear cross-section of gold could then be determined. This has been measured in detail so that it is suitable for a benchmark. The target material Ra-226 was also measured, using a target capsule made of aluminium. At the end of the project, a small amount of Ra-226 was irradiated and the yield of Ac-225 was determined. 

Subproject B: In the second half of the project, the focus was placed on the construction of a prototype for a bremsstrahlung converter that can absorb a beam power of 100 kW. In the first part, the framework conditions were set and the limiting factors determined on this basis, with the aid of Monte Carlo simulations in order to understand the energy density and the production rate of the bremsstrahlung in detail. This allowed the selection of materials to be limited on the basis of physical and manufacturing properties. Due to the high energy density, a rotating disk was identified early on as the basic approach, and water was chosen for cooling. Based on these general conditions, the concept of a Tesla converter was developed and studied. Here, several disks are rotated in series, creating a so-called Tesla pump (or disk rotor pump). The disks are made of tungsten to ensure an optimum yield of bremsstrahlung photons. The behaviour of the disks under load was simulated in detail. Based on the findings from Monte Carlo, flow and FEM simulations, a prototype and a cooling circuit were designed and realized. In final tests on the electron accelerator, the photon yield was compared with a conventional converter and the cooling performance was checked. Both results were in line with expectations.

Subproject C: Since the start of the project, around 60 samples have been irradiated for the research and improvement of radiochemical processes. Titanium, zinc, neodymium and radium were activated, among others. Detailed studies of separation possibilities and subsequent labelling was undertaken by the University of Bern. With the completion of the dedicated irradiation line, the yield could later be significantly increased. Within this setup, detailed studies were carried out on the construction of a bremsstrahlung converter; this included Monte Carlo, FEM and flow simulations.

Publikationen / Ergebnisse (Englisch)

- International Symposium on Trends in Radiopharmaceuticals (ISTR-2019), 28 October–1 November 2019, Vienna, Austria
- Präsentation METAS Seminar, 25.November 2020

- PRISMAP Public Evnet, 22 Nov 2022, INFN Legnaro, Poster: Conceptual Design of a High Power Bremsstrahlung Converter for Radioisotope Production

- Patentanmeldung, 23159029.0 – 1212, 2023, High Power Point-source Converter Target Assembly, Related Facility and Method to Produce Bremsstrahlung for Photonuclear Reactions using an Electron Linear Accelerator or an Electron Accelerator with Similar Time Structure of the Beam, Türler Andreas, Lüthi Matthias

- Patentanmeldung, PCT/EP2022/084449, 2022, High Power Converter Target Assembly, Related Facility and Method to Produce Bremsstrahlung for Photonuclear Reactions, Türler Andreas, Vagheian Mehran, Lüthi Matthias

- Braccini, S., Casolaro, P., Dellepiane, G., Kottler, C., Lüthi, M., Mercolli, L., Peier, P., Scampoli, P., & Türler, A. (2023). Methodology for measuring photonuclear reaction cross sections with an electron accelerator based on Bayesian analysis (Version 1). arXiv. https://doi.org/10.48550/ARXIV.2309.11270

- Xiuyun Chai, Mohamed F. Nawar, Matthias Lüthi, Ronald Zingg, and Andreas Türler, (2023). Development of a Separation Method for the Medical Radionuclide 47Sc from Bulk Amounts of Titanium, JNRC