Elastin-like polypeptides in radiopharmaceutical delivery: current evidence, design principles, and translational challenges

Elastin-like polypeptides (ELPs) are genetically engineered protein polymers with tunable sequences, molecular weights, phase-transition temperatures, and functional sites. Their programmable and thermoresponsive properties allow control over solubility, self-assembly, and local retention, supporting their use as carriers for radiopharmaceutical delivery. This review summarises ELP properties relevant to nuclear medicine and discusses radioiodination, radiometal chelation, site-specific conjugation, and self-assembly-based loading. It also examines three main delivery modes: systemic delivery, thermally triggered lesion enrichment, and local in situ depot formation. We discuss how molecular design, labelling chemistry, formulation, and the route of administration affect radiochemical stability, biodistribution, and dose deposition. Potential applications include tumour imaging, radionuclide therapy, and multimodal treatment. Important challenges include preserving ELP function after labelling, maintaining in vivo stability, and establishing scalable manufacturing and quality-control procedures. Biosafety, immunogenicity, repeat-dose effects, and regulatory requirements also require systematic evaluation. Continued optimisation may support the development of ELP-based systems for controlled radionuclide delivery and cancer theranostics.