Kinetic Modeling of the Serotonin 5-HT1B Receptor Radioligand 11CP943 in Humans

(11)CP943 is a new radioligand recently developed to image and quantify serotonin 5-Hydroxytryptamine (5-HT(1B)) receptors with positron emission tomography (PET). The purpose of this study was to evaluate (11)CP943 for this application in humans, and to determine the most suitable quantification method. Positron emission tomography data and arterial input function measurements were acquired in a cohort of 32 human subjects. Using arterial input functions, compartmental modeling, the Logan graphical analysis, and the multilinear method MA1 were tested. Both the two tissue-compartment model and MA1 provided good fits of the PET data and reliable distribution volume estimates. Using the cerebellum as a reference region, BP(ND) binding potential estimates were computed. (11)CP943 BP(ND) estimates were significantly correlated with in vitro measurements of the density of 5-HT(1B) receptors, with highest values in the occipital cortex and pallidum. To evaluate noninvasive methods, two- and three-parameter graphical analyses, Simplified Reference Tissue Models (SRTM and SRTM2), and Multilinear Reference Tissue Models (MRTM and MRTM2) were tested. The MRTM2 model provided the best correlation with MA1 binding-potential estimates. Parametric images of the volume of distribution or binding potential of (11)CP943 could be computed using both MA1 and MRTM2. The results show that (11)CP943 provides quantitative measurements of 5-HT(1B) binding potential.