Strategic Objectives of Nanotechnology-Driven Repurposing in Radiopharmacy. Implications for Radiopharmaceutical Repurposing (Beyond Oncology)

The integration of nanotechnology into drug repurposing strategies is redefining the development landscape for diagnostic, therapeutic, and theranostic agents. Originally based on radiopharmaceuticals, many of these nanoplatforms evolve into multifunctional systems by incorporating additional imaging modalities (e.g., MRI, fluorescence) or non-radioactive therapies (e.g., photodynamic therapy, chemotherapy). These hybrid constructs often emerge from the reformulation, repositioning, or revival of previously approved or abandoned compounds, generating entities with novel pharmacological, pharmacokinetic, and biodistribution profiles. However, their translational potential faces significant regulatory hurdles. Existing frameworks—typically designed for single-modality drugs or devices—struggle to accommodate the combined complexity of nanoengineering, radioactive components, and integrated functionalities. This review examines how these systems challenge current norms in classification, safety assessment, preclinical modeling, and regulatory coordination. It also addresses emerging concerns around digital adjuncts such as AI-assisted dosimetry and software-based therapy planning. Finally, the article outlines international initiatives aimed at closing regulatory gaps and provides future directions for building harmonized, risk-adapted frameworks that support innovation while ensuring safety and efficacy.