Steroidal Scaffolds in Radiopharmaceutical Chemistry: Synthetic Strategies, Receptor Targeting, and Theranostic Applications

Advances in medicinal chemistry and molecular medicine have accelerated the development of targeted strategies that deliver bioactive agents selectively to diseased tissues. Targeted radionuclide therapy and nuclear imaging depend on pairing an appropriate radionuclide with a ligand that confers biological selectivity, and steroids are especially well suited to this role because their rigid tetracyclic scaffold supports specific interactions with protein binding sites and high-affinity recognition of estrogen, progesterone, and androgen receptors relevant to hormone-dependent cancers. This review provides a comprehensive radiochemical and medicinal chemistry overview of steroid-based radiopharmaceuticals, with emphasis on their use as targeting ligands and as platforms for incorporating diagnostic and therapeutic radionuclides. It surveys radiolabelling strategies involving fluorine-18, radioiodine, and radiometals, and discusses how synthetic methodology, bioconjugation, and structural modification influence receptor affinity, pharmacokinetics, radiochemical performance, and in vivo stability. The review also highlights clinically relevant examples such as 16α-[ 18 F]fluoroestradiol, whose uptake correlates strongly with estrogen receptor expression in tumour tissue, and examines emerging radiometal conjugates and theranostic concepts for precision oncology.