Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36: Test-retest reproducibility and head-to-head comparison with the antagonist [18F]altanserin

•[11C]Cimbi-36 demonstrated excellent reproducibility as a 5-HT2A receptor agonist PET radioligand in healthy volunteers.•In vivo binding of [11C]Cimbi-36 and [18F]altanserin was highly correlated demonstrating that they both image 5-HT2A receptors in the human brain•In choroid plexus and hippocampus, [11C]Cimbi-36 binding exceeded [18F]altanserin binding suggesting high density of 5-HT2C receptors here.•[11C]Cimbi-36 may be used to detect both 5-HT2A and 5-HT2C receptor binding in the human brain

Introduction[11C]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 [11C]Cimbi-36 PET and compare [11C]Cimbi-36 and the 5-HT2A receptor antagonist [18F]altanserin.MethodsSixteen healthy volunteers (mean age 23.9 ± 6.4 years, 6 males) were scanned twice with a high resolution research tomography PET scanner. All subjects were scanned after a bolus of [11C]Cimbi-36; eight were scanned twice to determine test-retest variability in [11C]Cimbi-36 binding measures, and another eight were scanned after a bolus plus constant infusion with [18F]altanserin. Regional differences in the brain distribution of [11C]Cimbi-36 and [18F]altanserin were assessed with a correlation of regional binding measures and with voxel-based analysis.ResultsTest-retest variability of [11C]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 [11C]Cimbi-36 and [18F]altanserin (mean Pearson's r: 0.95 ± 0.04) suggesting similar cortical binding of the radioligands. Relatively higher binding with [11C]Cimbi-36 as compared to [18F]altanserin was found in the choroid plexus and hippocampus in the human brain.ConclusionsExcellent test-retest reproducibility highlights the potential of [11C]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 [11C]Cimbi-36 binding likely represents binding to both 5-HT2A and 5-HT2C receptors.