Abstract:
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.
journal_name
Neuroimagejournal_title
NeuroImageauthors
Ettrup A,Svarer C,McMahon B,da Cunha-Bang S,Lehel S,Møller K,Dyssegaard A,Ganz M,Beliveau V,Jørgensen LM,Gillings N,Knudsen GMdoi
10.1016/j.neuroimage.2016.02.001subject
Has Abstractpub_date
2016-04-15 00:00:00pages
167-174eissn
1053-8119issn
1095-9572pii
S1053-8119(16)00097-5journal_volume
130pub_type
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