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 (via 212Bi). 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.

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