Targeted radioligand therapy in oncology: clinical development across targets and platforms

Radioligand therapy (RLT) has gained increasing prominence as an important therapeutic modality in oncology. By coupling a tumor-targeting ligand with a therapeutic radionuclide, therapeutic targeted RLT enables selective radiation delivery to a malignant site. Clinical validation of prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-directed therapies, together with the regulatory approvals of lutetium Lu 177 dotatate and lutetium Lu 177 vipivotide tetraxetan, has established proof of clinical utility for this approach and driven a broader expansion of RLT development across oncology. In this review, we outline the major emitter classes for therapeutic RLT, provide an overview of the active clinical development landscape with emphasis on different targeting strategies, discuss the toxicity considerations relevant to this modality, and conclude with a perspective on the major challenges and future directions shaping the field.