Estimation of neocortical serotonin-2 receptor binding potential by single-dose fluorine-18-setoperone kinetic PET...

Because it satisfies most of the characteristics required to quantify in vivo neocortical serotonin-2 (5HT2) receptors, 18F-setoperone was selected for use in PET estimation of the neocortical 5HT2 binding parameters in baboons according to a single-dose paradigm.

The neocortical binding potential (i.e., Bmax/KD or the k3/k4 ratio) was assessed by three different methods, with the cerebellum taken as the reference structure in all instances. Method 1 was based on a Logan-Patlak graphical analysis of both cerebellar and neocortical data, which allows estimation of the neocortical k3'/k4 ratio; it required a separate estimation of k5 and k6 from classical nonlinear least-squares (NLSQ) three-compartment modeling of cerebellar data. Method 2 was an original combination of a four-compartment Logan-Patlak procedure for neocortical data and an NLSQ three-compartment procedure for cerebellar data, allowing the neocortical k3/k4 ratio to be obtained directly. In Method 3, an NLSQ three-compartment procedure was applied to cerebellar data and an NLSQ four-compartment procedure to neocortical data, allowing separate determinations of k3 and k4 for the neocortex and, in turn, the k3/k4 ratio.

In all three methods, the arterial plasma input function was corrected for the presence of 18F-metabolites, and the vascular fraction was either fitted or fixed. Statistical analysis showed no significant difference among the k3/k4 values obtained from the three methods. Method 3 was the least stable because of an occasional poor NLSQ four-compartment fit on neocortical data. Method 2 provided the least cumbersome estimate of the k3/k4 ratio and was found easy and accurate for generating parametric maps of the 5HT2 binding potential.

This method might be useful in clinical investigations to provide quantitative assessment of receptor binding potential. In semiquantitative investigations, the neocortical-to-cerebellum pseudoequilibrium ratio may be adequate, as suggested by the significant correlations with measured k3/k4 ratios found here.