Purpose PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand 11 CPK-11195 limits accurate quantification. 18 FGE-180, a novel TSPO ligand, displays superior binding to 11 CPK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of 18 FGE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures. Methods Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of 18 FGE-180. Kinetic modelling of time–activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution ( V T ) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region. Results The two-tissue compartment model was the best model. The average regional delivery rate constant ( K 1 ) was 0.01 mL cm −3  min −1 indicating low extraction across the blood–brain barrier (1 %). The estimated median V T across all ROIs was also low, ranging from 0.16 mL cm −3 in the striatum to 0.38 mL cm −3 in the thalamus. There were no significant differences in V T between HABs and MABs across all ROIs. Conclusion A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low V T estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of 18 FGE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of TSPO expression.