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J Cereb Blood Flow Metab. 2010 Jan;30(1):196-210. doi: 10.1038/jcbfm.2009.195. Epub 2009 Sep 23.

Kinetic modeling of the serotonin 5-HT(1B) receptor radioligand [(11)C]P943 in humans.

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PET Center, Department of Diagnostic Radiology, Yale University, New Haven, Connecticut, USA.


[(11)C]P943 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)C]P943 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)C]P943 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)C]P943 could be computed using both MA1 and MRTM2. The results show that [(11)C]P943 provides quantitative measurements of 5-HT(1B) binding potential.

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