[Carbonyl-¹¹C]WAY-100635 is a promising PET radioligand for the 5-HT_1Areceptor, having demonstrated more favorable characteristics forin vivoimaging than the previously available [O-methyl-¹¹C]WAY-100635. The current study evaluates different tracer kinetic modelling strategies for the quantification of 5-HT_1Areceptor binding in human brain. Mathematical modelling of the carbonyl-labeled radiotracer is investigated using compartmental structures, including both plasma input and reference tissue approaches. Furthermore, the application of basis function methods allows for the investigation of parametric imaging, providing functional maps of both delivery and binding of the radioligand. Parameter estimates of binding from normal volunteers indicate a low intra- versus a high intersubject variability. It is concluded that a simplified reference tissue approach may be used to quantify 5-HT_1Abinding either in terms of ROI data or as parametric images.