Advancements in Targeted Radiopharmaceuticals: Innovations in Diagnosis and Therapy for Enhanced Cancer Management

Radiopharmaceuticals (RPhs) represent a breakthrough in nuclear medicine due to their ability to provide precise diagnosis and targeted therapy for cancer by incorporating radioactive isotopes into carrier molecules. This review systematically discusses the recent advances in the development of RPhs, focusing on state‐of‐the‐art probe design strategies and click chemistry applications that accelerate RPh syntheses and improve targeting efficiency. The manuscript synthesizes literature from multiple databases spanning January 2014 to April 2025, encompassing diagnostic modalities including positron emission tomography (PET) and single‐photon emission computed tomography (SPECT) imaging, and therapeutic applications utilizing alpha and beta emitters such as 225 Ac and 177 Lu. Clinically approved agents, such as 177 Lu‐DOTATATE and 177 Lu‐PSMA‐617, are used for neuroendocrine tumors and metastatic castration‐resistant prostate cancer, respectively, with significant therapeutic efficacy. The review focuses on new targets, such as fibroblast activation protein, CXCR4 chemokine receptors, and gastrin‐releasing peptide receptors, and new delivery systems using nanotechnology to improve biodistribution and tumor accumulation. Challenges regarding production scalability, regulatory frameworks, and integrating artificial intelligence for personalized dosimetry and treatment planning remain crucial. Combination therapeutic approaches using targeted radionuclide therapy (TRT) in synergy with chemotherapy and immunotherapy and external beam radiation are showing promising results in refractory cancers. The potential avenues include theranostics, predictive modeling for patient selection, and new molecular targeting strategies. This review highlights the transformative potential of RPhs in precision oncology, providing an overview of the current clinical applications and future research trajectories toward improved cancer management.