Visualizing reactive astrocytes: Positron emission tomography imaging ligands for imidazoline‐2 binding sites

Abstract Imidazoline‐2 binding sites (I 2 BS) exhibit specific expression in reactive astrocytes of the brain and are implicated in various pathophysiological processes, including analgesia, inflammation, Alzheimer's disease, Parkinson's disease, and glial tumors. However, the lack of available protein structural data poses a challenge in the exploration of I 2 BS functions and pharmacological characterizations, indicating the need for the discovery of selective ligands. As a non‐invasive and translational molecular imaging tool, positron emission tomography (PET) has found wide application in clinical diagnosis and drug discovery. Consequently, several PET ligands have been developed to “visualize” I 2 BS in the living brain, thereby elucidating the biological implications of I 2 BS and facilitating I 2 BS‐directed drug development. This review offers a comprehensive update on I 2 BS PET ligands, with a focus on their chemotypes and PET imaging outcomes. Furthermore, the review provides a summary of recent I 2 BS drug discoveries, which could serve as a catalyst for the development of more potent PET ligands.