CHAPTER 11: Metal-based Radiotherapeutics

In nuclear medicine, the transition from statistical and population-based care to individual and personalized medicine enables numerous enhancements to the standard-of-care in cancer therapy. In this context, an expanding lineup of radionuclides with various decay properties and chemistry allows for precise alignment of these aspects with the biology and pharmacokinetics of molecular targeting agents. Indeed, the application of radionuclide-based therapeutics and companion imaging agents have seen dramatic improvements in recent decades – considerable advances have been made at every stage of radiopharmaceutical development which has provided improved isotope availability, in vivo stability, target specificity, and reduced toxicity. Especially with regard to radiotherapeutic agents, progress in these areas has been largely dominated by the radiometals. The anti-cancer function of radiotherapeutic pharmaceuticals is mechanistically different from those used in chemotherapeutic intervention. The first portion of this chapter aims to provide an abbreviated but adequate discussion of the various types of therapeutically relevant decay modes and the dominant radiobiological effects of their corresponding radiations. The remaining portion of this chapter investigates specific radionuclides, how their unique properties are leveraged within clinically and preclinically promising therapeutic strategies, and also addresses critical barriers to implementation of each nuclide in research or clinical practice.