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


ABSTRACT: [(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.

SUBMITTER: Gallezot JD 

PROVIDER: S-EPMC2949107 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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

Gallezot Jean-Dominique JD   Nabulsi Nabeel N   Neumeister Alexander A   Planeta-Wilson Beata B   Williams Wendol A WA   Singhal Tarun T   Kim Sunhee S   Maguire R Paul RP   McCarthy Timothy T   Frost J James JJ   Huang Yiyun Y   Ding Yu-Shin YS   Carson Richard E RE  

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20090923 1


[(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 g  ...[more]

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