The Curies’ element: state of the art and perspectives on the use of radium in nuclear medicine

Background: The alpha-emitter radium-223 (Ra-223) is presently used in nuclear medicine for the palliative treatment of bone metastases from castration-resistant prostate cancer. This application arises from its advantageous decay properties and its intrinsic ability to accumulate in regions of high bone turnover when injected as a simple chloride salt. The commercial availability of [Ra-223]RaCl2 as a registered drug (Xofigo (R)) is a further additional asset. Main body: The prospect of extending the utility of Ra-223 to targeted alpha-therapy of non-osseous cancers has garnered significant interest. Different methods, such as the use of bifunctional chelators and nanoparticles, have been explored to incorporate Ra-223 in proper carriers designed to precisely target tumor sites. Nevertheless, the search for a suitable scaffold remains an ongoing challenge, impeding the diffusion of Ra-223-based radiopharmaceuticals. Conclusion: This review offers a comprehensive overview of the current role of radium radioisotopes in nuclear medicine, with a specific focus on Ra-223. It also critically examines the endeavors conducted so far to develop constructs capable of incorporating Ra-223 into cancer-targeting drugs. Particular emphasis is given to the chemical aspects aimed at providing molecular scaffolds for the bifunctional chelator approach.