Abstract
BACKGROUND: The alpha-emitter radium-223 ((223)Ra) 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 [(223)Ra]RaCl(2) as a registered drug (Xofigo(®)) is a further additional asset. MAIN BODY: The prospect of extending the utility of (223)Ra to targeted α-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 (223)Ra in proper carriers designed to precisely target tumor sites. Nevertheless, the search for a suitable scaffold remains an ongoing challenge, impeding the diffusion of (223)Ra-based radiopharmaceuticals. CONCLUSION: This review offers a comprehensive overview of the current role of radium radioisotopes in nuclear medicine, with a specific focus on (223)Ra. It also critically examines the endeavors conducted so far to develop constructs capable of incorporating (223)Ra into cancer-targeting drugs. Particular emphasis is given to the chemical aspects aimed at providing molecular scaffolds for the bifunctional chelator approach.