Periodic Reporting for period 2 - SECURE (Strengthening the European Chain of sUpply for next generation medical RadionuclidEs)
Okres sprawozdawczy: 2024-04-01 do 2025-09-30
Targeted radionuclide therapy (TRT) has become increasingly prominent in nuclear medicine. Radiopharmaceuticals based on beta-emitters, such as Lu-177, have proven highly efficient in treating patients with metastatic neuroendocrine tumors or advanced prostate cancer. Furthermore, alpha-emitters have also been adopted into clinical practice. Currently, the demand for both established and emerging radionuclides for TRT is increasing rapidly. However, this is not equally matched by increased radionuclide availability or by addressing related technical gaps. These include emerging beta-emitters like Tb-161, alpha-emitting radionuclides, such as Ac-225 and Pb-212/Bi-212, for Targeted Alpha Therapy (TAT). Therefore, the SECURE consortium has teamed up to strengthen the EU supply network and enhance the availability and sustainability of radionuclides in the EU.
Selected radionuclides: Ag-111, Tb-161, Lu-177, Re-188, and Au-199 as beta-emitters, and Ac-225 and Pb-212 as alpha-emitters, with high potential for TRT, were in focus of the SECURE project, in their entire life cycle assessment, starting from the resourcing, available irradiation facilities, target preparation and handling, target encapsulation, processing, and their use in the preparation of radiopharmaceuticals. Alternative solutions were investigated, such as the use of legacy materials. Mitigating the limited availability of enriched target materials was addressed by the example of Cu-64. The objective of SECURE was to address gaps and challenges in securing their future availability, including:
- Developments in innovative routes of production of selected radionuclides, involving research reactors and other neutron sources as well as charged-particle accelerators, separation/purification methods, legacy materials, generators, and transportation concerns,
- Developments in irradiation targets, target requirements, preparation and recycling procedures, and infrastructural needs, as well as target material sourcing and target enrichment concerns,
- Assessment of radiation risks for the workers, patients, and caregivers related to the novel radionuclides and recommendations for their safe handling. Recommendations for implementing clinical trials involving radiopharmaceuticals, including the development of individual/specific organ dosimetry for therapeutic applications.
Meeting these objectives was demonstrated by the project results and supported by scientific publications. Proving the scalability of the results is underway.
Selected radionuclides: Ag-111, Tb-161, Lu-177, Re-188, and Au-199 as beta-emitters, and Ac-225 and Pb-212 as alpha-emitters, with high potential for TRT, were in focus of the SECURE project, in their entire life cycle assessment, starting from the resourcing, available irradiation facilities, target preparation and handling, target encapsulation, processing, and their use in the preparation of radiopharmaceuticals. Alternative solutions were investigated, such as the use of legacy materials. Mitigating the limited availability of enriched target materials was addressed by the example of Cu-64. The objective of SECURE was to address gaps and challenges in securing their future availability, including:
- Developments in innovative routes of production of selected radionuclides, involving research reactors and other neutron sources as well as charged-particle accelerators, separation/purification methods, legacy materials, generators, and transportation concerns,
- Developments in irradiation targets, target requirements, preparation and recycling procedures, and infrastructural needs, as well as target material sourcing and target enrichment concerns,
- Assessment of radiation risks for the workers, patients, and caregivers related to the novel radionuclides and recommendations for their safe handling. Recommendations for implementing clinical trials involving radiopharmaceuticals, including the development of individual/specific organ dosimetry for therapeutic applications.
Meeting these objectives was demonstrated by the project results and supported by scientific publications. Proving the scalability of the results is underway.
Several production routes for alpha emitters such as Pb-212 and Ac-225 depend on access to source materials, which are often byproducts of the civil nuclear, mining, or medical industries. One route to Pb-212 explored at the UKNNL relies on access to irradiated uranium (containing U-232), which has been reprocessed to a high purity level. Another route to Th-227 and Ra-223 involved a material generated as a byproduct from a uranium refinery. The main considerations for retrieving these sources from legacy materials are that the desired radionuclide is sufficiently concentrated for feasible extraction and that contaminant radionuclides can be separated so as not to affect the purity of the product alpha emitter.
The novel gas-mediated Pb-212 generator based on Th-228 enables reliable daily production of high-purity Pb-212 with minimal Th-228 source losses, ensuring sustainable long-term operation. The flexible sourcing of Th-228 from both reactor and non-reactor routes strengthens supply chain resilience, while the compact design allows decentralized implementation in hospitals, radiopharmacies, or central production sites. Demonstrated production at tens of MBq already supports preclinical research, and the system is readily scalable to GBq levels for clinical and commercial use, providing a secure and scalable supply route for Pb-212-based therapeutics.
The question of how to make the W-188/Re-188 generators viable was addressed by the development of dissolution methods for irradiated WO₃ targets and neutronics calculations supporting scaling up the mass of irradiated WO₃. The high-activity R&D radionuclide generator W-188/Re-188 increases the availability of Re-188, supporting research on its applications.
To support the processes associated with generating and using medical radionuclides, the Computational Assessment of Radionuclide Production (CARP) developments were validated using partner data, bringing them to the higher Technology Readiness Levels, towards commercialisation.
The achievements related to the radiation protection and safe handling of novel radionuclides include the development of (i) a Life Cycle Assessment (LCA) methodology to evaluate radiation protection across all stages of TAT-radionuclide production, and (ii) a platform for dosimetry optimisation of TAT. Both were based on the findings of the report on the current state of the art in clinical applications for radionuclide therapies.
The LCA covers routine and unintended exposures to workers, caregivers, and the public via external irradiation, inhalation, ingestion, and skin contamination. A benchmark study revealed large dose variations across radionuclides and production pathways, highlighting the importance of process design in minimizing risk, waste, and inefficient use of materials, and allowed formulation of recommendations on comprehensive LCAs, optimizing production, prioritizing inhalation and ingestion protection, managing external radiation, including caregiver/public exposure, and following the hierarchy of safety controls. Future work should establish standardized LCA methodologies and practical guidance.
The novel gas-mediated Pb-212 generator based on Th-228 enables reliable daily production of high-purity Pb-212 with minimal Th-228 source losses, ensuring sustainable long-term operation. The flexible sourcing of Th-228 from both reactor and non-reactor routes strengthens supply chain resilience, while the compact design allows decentralized implementation in hospitals, radiopharmacies, or central production sites. Demonstrated production at tens of MBq already supports preclinical research, and the system is readily scalable to GBq levels for clinical and commercial use, providing a secure and scalable supply route for Pb-212-based therapeutics.
The question of how to make the W-188/Re-188 generators viable was addressed by the development of dissolution methods for irradiated WO₃ targets and neutronics calculations supporting scaling up the mass of irradiated WO₃. The high-activity R&D radionuclide generator W-188/Re-188 increases the availability of Re-188, supporting research on its applications.
To support the processes associated with generating and using medical radionuclides, the Computational Assessment of Radionuclide Production (CARP) developments were validated using partner data, bringing them to the higher Technology Readiness Levels, towards commercialisation.
The achievements related to the radiation protection and safe handling of novel radionuclides include the development of (i) a Life Cycle Assessment (LCA) methodology to evaluate radiation protection across all stages of TAT-radionuclide production, and (ii) a platform for dosimetry optimisation of TAT. Both were based on the findings of the report on the current state of the art in clinical applications for radionuclide therapies.
The LCA covers routine and unintended exposures to workers, caregivers, and the public via external irradiation, inhalation, ingestion, and skin contamination. A benchmark study revealed large dose variations across radionuclides and production pathways, highlighting the importance of process design in minimizing risk, waste, and inefficient use of materials, and allowed formulation of recommendations on comprehensive LCAs, optimizing production, prioritizing inhalation and ingestion protection, managing external radiation, including caregiver/public exposure, and following the hierarchy of safety controls. Future work should establish standardized LCA methodologies and practical guidance.
The consortium developed and successfully validated:
- a process to separate no-carrier-added Au-199 (promising for SPECT imaging or beta therapy with Au-compounds) from reactor-irradiated Pt targets. This process is also foreseen to be exploited by ILL and NCBJ in the frame of the PRISMAP+ project (submitted).
- a small-scale W-188/W-188 generator that enables decentralized access to high-purity Re-188 for research and radiopharmaceutical development.
The recommendations on the safety aspects in the supply chain for the personalized planning and patient dosimetry protocols that should enhance the potential of radionuclide therapy as one of the major treatment techniques in cancer were developed.
Within SECURE, UKNNL has been working on a sustainable supply of Pb-212 from recycled nuclear fuel that has already been used to power homes across the country. Recently granted funding of £9.9m investment from the Innovate UK Sustainable Medicines Manufacturing Innovation Programme (SMMIP), backed by a further £8.9m from industry, will support a major project to develop cutting-edge new treatments for cancer. The project will use a radionuclide, Pb-212, to create TAT. https://uknnl.com/2025/11/uk-nuclear-revolution-powers-next-generation-precision-cancer-therapies/(odnośnik otworzy się w nowym oknie)
The platform for dosimetry optimisation was finalised by completing the simulation of PET and SPECT digital twins datasets and associated AI-based dose prediction. The platform was expanded to include Ac-225 dose estimation following its validation with clinical Lu-177-PSMA data. Ac-225 alpha therapy was investigated, comparing fixed and personalized dosing and demonstrating the capability of the platform through patient-specific dosimetry to minimise the dose to organs at risk in TAT.
- a process to separate no-carrier-added Au-199 (promising for SPECT imaging or beta therapy with Au-compounds) from reactor-irradiated Pt targets. This process is also foreseen to be exploited by ILL and NCBJ in the frame of the PRISMAP+ project (submitted).
- a small-scale W-188/W-188 generator that enables decentralized access to high-purity Re-188 for research and radiopharmaceutical development.
The recommendations on the safety aspects in the supply chain for the personalized planning and patient dosimetry protocols that should enhance the potential of radionuclide therapy as one of the major treatment techniques in cancer were developed.
Within SECURE, UKNNL has been working on a sustainable supply of Pb-212 from recycled nuclear fuel that has already been used to power homes across the country. Recently granted funding of £9.9m investment from the Innovate UK Sustainable Medicines Manufacturing Innovation Programme (SMMIP), backed by a further £8.9m from industry, will support a major project to develop cutting-edge new treatments for cancer. The project will use a radionuclide, Pb-212, to create TAT. https://uknnl.com/2025/11/uk-nuclear-revolution-powers-next-generation-precision-cancer-therapies/(odnośnik otworzy się w nowym oknie)
The platform for dosimetry optimisation was finalised by completing the simulation of PET and SPECT digital twins datasets and associated AI-based dose prediction. The platform was expanded to include Ac-225 dose estimation following its validation with clinical Lu-177-PSMA data. Ac-225 alpha therapy was investigated, comparing fixed and personalized dosing and demonstrating the capability of the platform through patient-specific dosimetry to minimise the dose to organs at risk in TAT.