Radionuclide theranostics: advances and clinical applications in lung cancer

Lung cancer remains a leading cause of global cancer deaths, underscoring the urgent need for more accurate diagnostic and treatment approaches. Radionuclide theranostics has rapidly emerged as a paradigm that couples molecular imaging with targeted internal irradiation, enabling personalized cancer care. This review provides a systematic overview of radionuclide theranostics in lung cancer. We first summarize core theranostic principles, including the classes of diagnostic and therapeutic radionuclides and their mechanisms of action. We then emphasize target selection, discussing key molecular targets overexpressed in lung tumors and within the tumor microenvironment that are suitable for radiopharmaceutical development. We synthesize clinical translational evidence by collating efficacy and safety outcomes from pivotal studies and highlighting candidate agents currently in clinical trials. We also examine patient stratification, combination strategies, and the management of treatment-related toxicities. Finally, we outline major challenges, such as target heterogeneity, uncertainties in optimal dosing, and incomplete toxicity profiling, and propose future directions to optimize ligand design, expand target and radionuclide repertoires, and integrate radionuclide therapy with other treatment modalities.