Comprehensive analysis of [18F]MFBG biodistribution normal patterns and variability in pediatric patients with neuroblastoma.
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PURPOSE: [18F]-meta-fluorobenzylguanidine ([18F]MFBG) PET/CT is a promising imaging modality for neural crest-derived tumors, particularly neuroblastoma. Accurate interpretation necessitates an understanding of normal biodistribution and variations in physiological uptake. This study aimed to systematically characterize the physiological distribution and variability of [18F]MFBG uptake in pediatric patients to enhance clinical interpretation and differentiate normal from pathological uptake. METHODS: We retrospectively analyzed [18F]MFBG PET/CT scans from 169 pediatric neuroblastoma patients, including 20 in confirmed remission, for detailed biodistribution analysis. Organ uptake was quantified using both manual segmentation and deep learning(DL)-based automatic segmentation methods. Patterns of physiological uptake variants were categorized and illustrated using representative cases. RESULTS: [18F]MFBG demonstrated consistent physiological uptake in the salivary glands (SUVmax 9.8 ± 3.3), myocardium (7.1 ± 1.7), and adrenal glands (4.6 ± 0.9), with low activity in bone (0.6 ± 0.2) and muscle (0.8 ± 0.2). DL-based analysis confirmed uniform, mild uptake across vertebral and peripheral skeletal structures (SUVmean 0.47 ± 0.08). Three physiological liver uptake patterns were identified: uniform (43%), left-lobe predominant (31%), and marginal (26%). Asymmetric uptake in the pancreatic head, transient brown adipose tissue activity, gallbladder excretion, and symmetric epiphyseal uptake were also recorded. These variants were not associated with structural abnormalities or clinical recurrence and showed distinct patterns from pathological lesions. CONCLUSION: This study establishes a reference for normal [18F]MFBG biodistribution and physiological variants in children. Understanding these patterns is essential for accurate image interpretation and the avoidance of diagnostic pitfalls in pediatric neuroblastoma patients.