Emerging Theranostic Radiometals (¹⁴⁹Tb, ⁴⁴Sc, ⁵²Mn, ²⁰³Pb, ⁵⁵Co)-Decay Diversity, Production Landscape, and Translational Imaging.

Abstract

Emerging metallic radionuclides are expanding theranostic capabilities in nuclear medicine by improving diagnostic sensitivity, enabling dosimetry, and matched theranostic approaches. ¹⁴⁹Tb, ⁴⁴Sc, ⁵²Mn, ²⁰³Pb, and ⁵⁵Co offer distinct nuclear decay properties, including extended half-lives, variable positron emissions, and prompt γ-photons that may influence quantitative imaging performance. Cyclotron and generator routes integrating enriched targets and optimized separations support clinical-scale supply, while advances in chelation chemistry improve in vivo stability and imaging performance. Preclinical and early clinical data demonstrate that ¹⁴⁹Tb provides intrinsic α-therapy and PET imaging capability for theranostic use, ⁴⁴Sc enables extended imaging relative to ⁶⁸Ga, supporting delayed imaging and improved tumor-to-background contrast for peptide-based radiopharmaceuticals and theranostic applications. ⁵²Mn supports prolonged biological tracking for antibody- and engineered-protein-targeted studies, whereas ²⁰³Pb serves as a diagnostic surrogate for ²¹²Pb based α-therapy (via²¹²Bi). ⁵⁵Co PET imaging supports the development and evaluation of 58mCo Auger electron therapy. Current challenges include limited global availability of highly enriched targets, management of long-lived radioactive by-products, and the need for standardized dosimetry and regulatory pathways to ensure reproducibility and safety. Ongoing developments in automated target handling, optimized separations, next-generation chelators, and harmonized regulation may facilitate broader clinical translation.