Kinetic modeling of the serotonin 5-HT 1B receptor radioligand 11 CP943 in humans

Jean Dominique Gallezot, Nabeel Nabulsi, Alexander Neumeister, Beata Planeta-Wilson, Wendol A. Williams, Tarun Singhal, Sunhee Kim, R. Paul Maguire, Timothy McCarthy, J. James Frost, Yiyun Huang, Yu Shin Ding, Richard E. Carson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)196-210
Number of pages15
JournalJournal of Cerebral Blood Flow and Metabolism
Volume30
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • 5-HT1B serotonin receptors
  • Brain
  • Evaluation of new radiotracers
  • Human
  • Positron emission tomography (PET)
  • Tracer kinetic modeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Fingerprint Dive into the research topics of 'Kinetic modeling of the serotonin 5-HT 1B receptor radioligand 11 CP943 in humans'. Together they form a unique fingerprint.

  • Cite this

    Gallezot, J. D., Nabulsi, N., Neumeister, A., Planeta-Wilson, B., Williams, W. A., Singhal, T., Kim, S., Maguire, R. P., McCarthy, T., Frost, J. J., Huang, Y., Ding, Y. S., & Carson, R. E. (2010). Kinetic modeling of the serotonin 5-HT 1B receptor radioligand 11 CP943 in humans. Journal of Cerebral Blood Flow and Metabolism, 30(1), 196-210. https://doi.org/10.1038/jcbfm.2009.195