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

Introduction: [C-11] 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 [C-11] Cimbi-36 PET and compare [C-11] Cimbi-36 and the 5-HT2A receptor antagonist [F-18] altanserin. Methods: Sixteen 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 [C-11] Cimbi-36; eight were scanned twice to determine test-retest variability in [C-11] Cimbi-36 binding measures, and another eight were scanned after a bolus plus constant infusion with [F-18] altanserin. Regional differences in the brain distribution of [C-11] Cimbi-36 and [F-18] altanserin were assessed with a correlation of regional binding measures and with voxel-based analysis. Results: Test-retest variability of [C-11] Cimbi-36 non-displaceable binding potential (BPND) was consistently <5% in high-binding regions and lower for reference tissuemodels as compared to a 2-tissue compartmentmodel. We found a highly significant correlation between regional BP(ND)s measuredwith [C-11] Cimbi-36 and [F-18] altanserin (mean Pearson's r: 0.95 +/- 0.04) suggesting similar cortical binding of the radioligands. Relatively higher binding with [C-11] Cimbi-36 as compared to [F-18] altanserin was found in the choroid plexus and hippocampus in the human brain. Conclusions: Excellent test-retest reproducibility highlights the potential of [C-11] 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 [C-11] Cimbi-36 binding likely represents binding to both 5-HT2A and 5-HT2C receptors. (C) 2016 Elsevier Inc. All rights reserved.