Non-invasive quantification of ¹⁸F-florbetaben with total-body EXPLORER PET

Purpose: Kinetic modeling of F-18-florbetaben provides important quantification of brain amyloid deposition in research and clinical settings but its use is limited by the requirement of arterial blood data for quantitative PET. The total-body EXPLORER PET scanner supports the dynamic acquisition of a full human body simultaneously and permits noninvasive image-derived input functions (IDIFs) as an alternative to arterial blood sampling. This study quantified brain amyloid burden with kinetic modeling, leveraging dynamic F-18-florbetaben PET in aorta IDIFs and the brain in an elderly cohort. Methods: F-18-florbetaben dynamic PET imaging was performed on the EXPLORER system with tracer injection (300 MBq) in 3 individuals with Alzheimer's disease (AD), 3 with mild cognitive impairment, and 9 healthy controls. Image-derived input functions were extracted from the descending aorta with manual regions of interest based on the first 30 seconds after injection. Dynamic time-activity curves (TACs) for 110 minutes were fitted to the two-tissue compartment model (2TCM) using population-based metabolite corrected IDIFs to calculate total and specific distribution volumes (V-T, V-s) in key brain regions with early amyloid accumulation. Non-displaceable binding potential (BPND) was also calculated from the multi-reference tissue model (MRTM). Results: Amyloid-positive (AD) patients showed the highest V-T and V-S in anterior cingulate, posterior cingulate, and precuneus, consistent with BPND analysis. BPND and V-T from kinetic models were correlated (r(2) = 0.46, P<2e(-16)) with a stronger positive correlation observed in amyloid-positive participants, indicating reliable model fits with the IDIFs. V-T from 2TCM was highly correlated (r(2) = 0.65, P< 2e(-16)) with Logan graphical V-T estimation. Conclusion: Non-invasive quantification of amyloid binding from total-body F-18-florbetaben PET data is feasible using aorta IDIFs with high agreement between kinetic distribution volume parameters compared to BPND in amyloid-positive and negative older individuals.