Incidental Findings in Asymptomatic Healthy Individuals Screened with Total-Body Ultra-Low-Dose 18F-FDG-PET/Low-Dose CT

OBJECTIVES: To evaluate the prevalence and clinical significance of incidental findings (IF) detected by Total-body 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in a genuinely asymptomatic cohort of blood donors. METHODS: 117 healthy, asymptomatic blood donors underwent ultra-low-dose FDG-PET/low-dose CT. The primary objective was to create an atlas of glucose metabolism in healthy individuals. A secondary objective was to assess the frequency and nature of IF, informing future considerations of the clinical value of potential screening programs. Here we report on IF. RESULTS: IF were detected in 64 participants (55%), with 51 (44%) presenting clinically insignificant IF and 13 (11%) clinically significant IF. Common insignificant IF included benign or inflammatory metabolic activity in the esophagus or lung parenchyma (n = 19), metabolically active reactive lymph nodes (n = 14), and degenerative skeletal changes (n = 13). Clinically significant IF comprised pathologically metabolically active cysts and polyps (n = 8), significantly enlarged vessels (n = 1), suspected malignant tumors (n = 1), large lipomas (n = 1), sarcoidosis (n = 1), and liver steatosis (n = 1). CONCLUSIONS: This is the first study to systematically investigate incidental findings in an asymptomatic cohort using ultra-low-dose total-body FDG-PET/CT. Even in this highly selected population, numerous IFs were revealed, underscoring the need for risk-stratified, data-driven screening strategies integrating genetic biomarkers identifying individuals who will truly benefit. ADVANCES IN KNOWLEDGE: This first study of ultra-low-dose total-body FDG-PET/CT in asymptomatic donors found frequent incidental findings (55%, 11% clinically significant), establishing lower-bound estimates and supporting risk-stratified screening approaches.