Next‑generation theranostic radiopharmaceuticals: Integrating alpha emitters and nanocarriers for precision oncology

Background Alpha-emitting radionuclides, characterized by high-linear energy transfer (LET) and short path length, are emerging as potent tools in targeted cancer therapy. When combined with advanced nanocarrier platforms, they enable precise tumor targeting, improved pharmacokinetics, and integrated diagnostic therapeutic (theranostic) applications. Objective This review aims to comprehensively evaluate the current status and future prospects of integrating alpha emitters with nanocarrier systems for precision oncology, with a focus on technological innovations, clinical translation, and regulatory considerations. Methods A targeted literature search (2024–2025) was conducted across PubMed, Scopus, and Web of Science, emphasizing peer-reviewed studies from high-impact journals. Key thematic areas include alpha-emitter characteristics, nanocarrier design, radiochemistry, tumor-targeting ligands, preclinical/clinical data, and manufacturing challenges. Results Commonly investigated α-emitters such as ^225Ac, ^211At, ^213Bi, and ^212Pb exhibit superior cytotoxic profiles compared to β-emitters, particularly in micro metastatic and resistant cancers. Nanocarrier systems liposomes, dendrimers, polymeric nanoparticles, and exosomes offer tunable physicochemical properties, ligand functionalization, and enhanced in vivo stability. Advances in chelation chemistry and cleavable linker strategies improve radiolabelling stability and isotopic purity. Preclinical studies demonstrate enhanced tumor uptake and reduced systemic toxicity, while early-phase clinical trials highlight safety and therapeutic promise. However, GMP-scale isotope production, dosimetry standardization, and regulatory harmonization remain critical bottlenecks. Conclusion Alpha-emitter Nanotheranostics represent a transformative approach in nuclear medicine, combining high-LET radiotoxicity with precision delivery. Overcoming manufacturing, regulatory, and logistical challenges will be essential for widespread clinical adoption. Emerging directions include AI-assisted nanocarrier optimization, hybrid theranostic formulations, and expansion into rare and refractory cancers, positioning these platforms as a cornerstone of personalized radiopharmaceutical oncology.