Recommendations on the Clinical Application and Future Potential of α-Particle Therapy. A Comprehensive Review of the Results from the SECURE Project

Background/Objectives The document comprehensively reviews the clinical applications and future potential of alpha-emitting radionuclides available for targeted alpha-particle therapy (TAT) in cancer treatment. The approval of radium-223 (Ra-223) therapy in 2013 marked a significant advancement in alpha-emitting therapeutic radiopharmaceuticals, which are primarily used in treatment of prostate cancer. The EU SECURE project was introduced as a major initiative to enhance the sustainability and safety of medical alpha-emitting radionuclides production in Europe. Methods: This literature review was conducted by a multidisciplinary team on selected radionuclides, including actinium-225, bismuth-213, astatine-211, lead-212, terbium-149, radium-22323 and thorium-227. These were selected based on their clinical significance, as identified in the EU PRISMAP project and subsequent literature searches. The review process involved searching major databases using specific keywords related to alpha-emitter therapy and was limited to articles in English. For each selected radionuclide, the physical characteristics, the radiochemistry, and the pre-clinical and clinical studies are explored. Results of the review show current and potential clinical applications of new alpha-emitting radionuclides, sharing insights from the SECURE consortium’s experiences and providing recommendations for future clinical trials to establish the therapeutic efficacy of these radionuclides. Conclusion: For each selected radionuclide, conclusion are reported in individual chapters. The results highlight the advantages of alpha particles in targeting cancer cells with minimal radiation to normal tissue, emphasising the need for high specificity and stability in delivery mechanisms, but also suggest that the full clinical potential of alpha particle therapy remains unexplored. Theranostic approach and dosimetric evaluations still represent relevant challenges.