Clinical applications of GLP-1 receptor–targeted PET imaging: A disease-oriented review

Glucagon-like peptide-1 receptor (GLP-1R)–targeted positron emission tomography (PET) imaging has gained increasing attention as a noninvasive approach for visualizing receptor expression and function in both physiological and pathological contexts. Owing to its highly specific expression in pancreatic β-cells and several extra-pancreatic tissues, GLP-1R provides a favorable target for radiotracer development, particularly using exendin-based ligands. This review provides a disease-oriented synthesis of current clinical and translational applications of GLP-1R PET, particularly with ⁶⁸ Ga- or ¹⁸ F-labeled exendin-4 analogs. GLP-1R PET has demonstrated high sensitivity in detecting insulinomas and shows promise in evaluating β-cell mass and receptor remodeling in diabetes and obesity. In type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), it enables noninvasive stratification of β-cell loss versus dysfunction. In obesity, receptor downregulation has been observed, and PET may aid in monitoring GLP-1R post-intervention restoration. In the central nervous system (CNS), while uptake in humans is limited, preclinical studies support imaging feasibility in neurodegenerative disease models. Continued tracer optimization and multimodal integration are needed to realize the full diagnostic and mechanistic potential of GLP-1R–targeted imaging.