Re-thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals

The potential and future role of certain metal radionuclides, for example, Sc-44, Zr-89, Y-86, Cu-64, Ga-68, Lu-177, Ac-225, and Bi-213, and several terbium isotopes has been controversially discussed in the past decades. Furthermore, the possible benefits of matched pairs of isotopes for tandem applications of diagnostics and therapeutics (theranostics) have been emphasized, while such approaches still have not made their way into routine clinical practice. Analysis of bibliographical data illustrates how popularity of certain nuclides has been promoted by cycles of availability and applications. We furthermore discuss the different practical requirements for diagnostic and therapeutic radiopharmaceuticals and the resulting consequences for efficient development of clinically useful pairs of radionuclide theranostics, with particular emphasis on the underlying economical factors. Based on an exemplary assessment of overall production costs for Ga-68 and F-18 radiopharmaceuticals, we venture a look into the future of theranostics and predict that high-throughput PET applications, that is, diagnosis of frequent conditions, will ultimately rely on F-18 tracers. PET radiometals will occupy a niche in the clinical low-throughput sector (diagnosis of rare diseases), but above all, dominate preclinical research and clinical translation. Matched isotope pairs will be of lesser relevance for theranostics but may become important for future PET-based therapeutic dosimetry.