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Region Hovedstaden - en del af Københavns Universitetshospital
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Serotonin 2A receptor agonist binding in the human brain with [(11)C]Cimbi-36: Test-retest reproducibility and head-to-head comparison with the antagonist [(18)F]altanserin

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INTRODUCTION: [(11)C]Cimbi-36 is a recently developed serotonin 2A (5-HT2A) receptor agonist positron emission tomography (PET) radioligand that has been successfully applied for human neuroimaging. Here, we investigate the test-retest variability of cerebral [(11)C]Cimbi-36 PET and compare [(11)C]Cimbi-36 and the 5-HT2A receptor antagonist [(18)F]altanserin.

METHODS: Sixteen healthy volunteers (mean age 23.9±6.4years, 6 males) were scanned twice with a high resolution research tomography PET scanner. All subjects were scanned after a bolus of [(11)C]Cimbi-36; eight were scanned twice to determine test-retest variability in [(11)C]Cimbi-36 binding measures, and another eight were scanned after a bolus plus constant infusion with [(18)F]altanserin. Regional differences in the brain distribution of [(11)C]Cimbi-36 and [(18)F]altanserin were assessed with a correlation of regional binding measures and with voxel-based analysis.

RESULTS: Test-retest variability of [(11)C]Cimbi-36 non-displaceable binding potential (BPND) was consistently <5% in high-binding regions and lower for reference tissue models as compared to a 2-tissue compartment model. We found a highly significant correlation between regional BPNDs measured with [(11)C]Cimbi-36 and [(18)F]altanserin (mean Pearson's r: 0.95±0.04) suggesting similar cortical binding of the radioligands. Relatively higher binding with [(11)C]Cimbi-36 as compared to [(18)F]altanserin was found in the choroid plexus and hippocampus in the human brain.

CONCLUSIONS: Excellent test-retest reproducibility highlights the potential of [(11)C]Cimbi-36 for PET imaging of 5-HT2A receptor agonist binding in vivo. Our data suggest that Cimbi-36 and altanserin both bind to 5-HT2A receptors, but in regions with high 5-HT2C receptor density, choroid plexus and hippocampus, the [(11)C]Cimbi-36 binding likely represents binding to both 5-HT2A and 5-HT2C receptors.

OriginalsprogEngelsk
TidsskriftNeuroImage
Vol/bind130
Sider (fra-til)167-74
Antal sider8
ISSN1053-8119
DOI
StatusUdgivet - 15 apr. 2016

ID: 46492679