Current Status and Perspectives of Novel Radiopharmaceuticals with Heterologous Dual-targeted Functions: 2013–2023

Radiotracers provide molecular- and cellular-level information in a noninvasive manner and have become important tools for precision medicine. In particular, the successful clinical application of radioligand therapeutic (RLT) has further strengthened the role of nuclear medicine in clinical treatment. The complicated microenvironment of the lesion has rendered traditional single-targeted radiopharmaceuticals incapable of fully meeting the requirements. The design and development of dual-targeted and multitargeted radiopharmaceuticals have rapidly emerged. In recent years, significant progress has been made in the development of heterologous dual-targeted radiopharmaceuticals. This perspective aims to provide a comprehensive overview of the recent progress in these heterologous dual-targeted radiopharmaceuticals, with a special focus on the design of ligand structures, pharmacological properties, and preclinical and clinical evaluation. Furthermore, future directions are discussed from this perspective.