Cyclic Peptides Radiopharmaceuticals: A Concise Review of Ligand Identification, Radiolabeling, and Clinical Progress

Radiopharmaceuticals are the foundation of nuclear medicine, with targeted ligands forming their core components. Peptide radiopharmaceuticals have demonstrated significant advantages in clinical practice and occupy a pivotal position among targeted radiopharmaceuticals approved by the FDA. Cyclic peptides represent an increasingly important class of radiopharmaceutical ligands, with remarkable progress achieved in recent years. Compared to linear peptides, they demonstrate greater targeting specificity and affinity, offering considerable potential for clinical translation. This article provides an overview of the general workflow and key considerations in the research and development of cyclic peptide radiopharmaceuticals, which includes the acquisition of cyclic peptide ligands, radionuclide labeling, and in vitro and in vivo studies. It outlines the major pre-clinical and clinical research advances in cyclic peptide radiopharmaceuticals and offers a prospective outlook on their future development. These developments highlight the promise of cyclic peptides to overcome key challenges in radiopharmaceutical development, such as improving tumor uptake/retention and pharmacodynamics. The aim is to provide a reference for professionals engaged in the development of novel radiopharmaceuticals, thereby accelerating innovation in radiopharmaceutical research and development.