Abstract Along with successful clinical approval of radiopharmaceuticals targeting somatostatin receptor subtype 2 and prostate‐specific membrane antigen, peptide‐based radiotracers have garnered the increasing attention in cancer imaging and theranostics. As a newly emerging targeting ligand in recent years, bicyclic peptides have demonstrated immense potential as a platform for radiotracers development, owing to distinct advantages including high affinity and specificity, druggability, favorable pharmacokinetics, rapid tissue penetration as well as high metabolic stability and bioavailability. In recent years, more and more bicyclic peptide‐based radiotracers have been explored through targeting of membrane type‐1 matrix metalloproteinase, Integrin α v β 3 , nectin cell adhesion molecule‐4, ephrin type‐A receptor 2, cluster of differentiation 38, cluster of differentiation 137, and programmed cell death ligand 1. Moreover, some of them have entered clinical trials, yielding encouraging results. This paper aims to summarize the cutting‐edge advances in the development of bicyclic peptide‐based radiotracers and offers a current landscape of their applications in cancer imaging and theranostics. Finally, the existing challenges in bicyclic peptide‐based radiotracers design, from target selection, ligand optimization to clinical translation, were further elaborated, providing a general guidance for development of next‐generation bicyclic peptide radiopharmaceuticals with clinical translational potentials.
Ou et al. (2026) studied this question.