Alpha-particle Emitting Radiopharmaceuticals in Targeted Therapy and Diagnostics: Challenges and Opportunities

Targeted Radionuclide Therapy (TRT) demonstrates significant therapeutic efficacy and survival benefits, especially for late-stage metastatic cancers with limited conventional therapy options. The majority of TRT radiopharmaceuticals rely on beta-emitting radionuclides, but more recently the global radiopharmaceutical community has come to appreciate the advantages of alpha-emitting radionuclides. Targeted alpha therapy (TAT) is now a fast-growing area of TRT, focused on the identification, development, and translation of alpha-emitting radiopharmaceuticals, several of which have started to show promising results in early-stage clinical trials. In this chapter, we provide an overview of the physical and chemical nature of alpha-emitting radionuclides relevant for the development and translation of TAT radiopharmaceuticals. Considerations for the production, chemistry, bioconjugation, and radiopharmaceutical formulation are all discussed to help equip the reader to better understand the cross-disciplinary physical, chemical, and biological factors that influence radiopharmaceutical development.