Purpose Tracer kinetic modeling of tissue time activity curves and the individual input function based on arterial blood sampling and metabolite correction is the gold standard for quantitative characterization of microglia activation by PET with the translocator protein (TSPO) ligand F-18-GE-180. This study tested simplified methods for quantification of F-18-GE-180 PET. Methods Dynamic F-18-GE-180 PET with arterial blood sampling and metabolite correction was performed in five healthy volunteers and 20 liver-transplanted patients. Population-based input function templates were generated by averaging individual input functions normalized to the total area under the input function using a leave-one-out approach. Individual population-based input functions were obtained by scaling the input function template with the individual parent activity concentration of F-18-GE-180 in arterial plasma in a blood sample drawn at 27.5 min or by the individual administered tracer activity, respectively. The total F-18-GE-180 distribution volume (V-T) was estimated in 12 regions-of-interest (ROIs) by the invasive Logan plot using the measured or the population-based input functions. Late ROI-to-whole-blood and ROI-to-cerebellum ratio were also computed. Results Correlation with the reference V-T (with individually measured input function) was very high for V-T with the population-based input function scaled with the blood sample and for the ROI-to-whole-blood ratio (Pearson correlation coefficient = 0.989 +/- 0.006 and 0.970 +/- 0.005). The correlation was only moderate for V-T with the population-based input function scaled with tracer activity dose and for the ROI-to-cerebellum ratio (0.653 +/- 0.074 and 0.384 +/- 0.177). Reference V-T, population-based V-T with scaling by the blood sample, and ROI-to-whole-blood ratio were sensitive to the TSPO gene polymorphism. Population-based V-T with scaling to the administered tracer activity and the ROI-to-cerebellum ratio failed to detect a polymorphism effect. Conclusion These results support the use of a population-based input function scaled with a single blood sample or the ROI-to-whole-blood ratio at a late time point for simplified quantitative analysis of F-18-GE-180 PET.