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

• Published in: NeuroImage (Orlando, Fla.) Vol. 130; pp. 167 - 174
• Main Authors: Ettrup, Anders, Svarer, Claus, McMahon, Brenda, da Cunha-Bang, Sofi, Lehel, Szabolcs, Møller, Kirsten, Dyssegaard, Agnete, Ganz, Melanie, Beliveau, Vincent, Jørgensen, Louise Møller, Gillings, Nic, Knudsen, Gitte Moos
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.04.2016; Elsevier Limited
• Subjects: 5-HT; Agonist; Agonists; Benzylamines - metabolism; Benzylamines - pharmacokinetics; Brain; Brain - metabolism; Carbon Radioisotopes - metabolism; Carbon Radioisotopes - pharmacokinetics; Choroid plexus; Cortex; Female; Fluorine Radioisotopes - metabolism; Fluorine Radioisotopes - pharmacokinetics; Hippocampus; Humans; Ketanserin - analogs & derivatives; Ketanserin - metabolism; Ketanserin - pharmacokinetics; LSD; Lysergic acid diethylamide; Male; Medical imaging; Neuroimaging; Neuroimaging - methods; Phenethylamines - metabolism; Phenethylamines - pharmacokinetics; Positron emission tomography; Positron-Emission Tomography - methods; Radioisotopes; Radiopharmaceuticals - metabolism; Radiopharmaceuticals - pharmacokinetics; Radiotracer evaluation; Receptor density; Reproducibility; Reproducibility of Results; Serotonin 5-HT2 Receptor Agonists - metabolism; Serotonin 5-HT2 Receptor Agonists - pharmacokinetics; Serotonin 5-HT2 Receptor Antagonists - metabolism; Serotonin 5-HT2 Receptor Antagonists - pharmacokinetics; Serotonin S2 receptors; Test–retest variability; Tomography; Young Adult; Neuroimaging; Agonist; 5-HT; Positron emission tomography; Radiotracer evaluation; Test–retest variability
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2016.02.001

[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. 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 [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. Test–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. Excellent 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. •[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