Quantitative β-Cell Mass Imaging Redefines Disease Staging and Glycemic Control in Type 1 Diabetes

Noninvasive measurement of pancreatic β-cell mass remains an important unmet need in type 1 diabetes because conventional surrogate markers, such as C-peptide, often lack sensitivity in advanced disease. This study evaluated the glucagon-like peptide 1 receptor-targeted positron emission tomography tracer, 18F-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4), to determine its ability to visualize pancreatic β-cell mass. Positron emission tomography/computed tomography performed at 60 and 120 min after tracer injection in individuals with type 1 diabetes was compared with data from healthy control participants. No serious adverse events occurred. Pancreatic uptake was consistently lower in individuals with type 1 diabetes and showed clear separation between individuals with insulin-dependent diabetes and healthy control participants at 120 min. Pancreatic uptake at 120 min correlated with fasting C-peptide index and inversely with hemoglobin A1c and daily insulin dose per body weight. These findings support [18F]FB(ePEG12)12-exendin-4 positron emission tomography/computed tomography as a noninvasive approach for assessing β-cell mass and disease status. ARTICLE HIGHLIGHTS: We undertook this study to address the persistent need for noninvasive assessment of β-cell mass in type 1 diabetes. We aimed to determine whether 18F-exendin positron emission tomography/computed tomography can reliably visualize residual β-cell mass and distinguish stages of disease. We found that pancreatic tracer uptake was consistently reduced in type 1 diabetes, differentiated insulin-dependent patients from control participants, and aligned with markers of β-cell function and glycemic status. Our findings suggest that 18F-exendin imaging may offer fundamental platform for disease staging, therapeutic monitoring, and individualized care.