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

Anders Ettrup; Claus Svarer; Brenda McMahon; Sofi da Cunha-Bang; Szabolcs Lehel; Kirsten Møller; Agnete Dyssegaard; Melanie Ganz; Vincent Beliveau; Louise Møller Jørgensen; Nic Gillings; Gitte Moos Knudsen

doi:10.1016/j.neuroimage.2016.02.001

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

Anders Ettrup, Claus Svarer, Brenda McMahon, Sofi da Cunha-Bang, Szabolcs Lehel, Kirsten Møller, Agnete Dyssegaard, Melanie Ganz, Vincent Beliveau, Louise Møller Jørgensen, Nic Gillings, Gitte Moos Knudsen

Department of Clinical Medicine

36 Citations (Scopus)

Abstract

Introduction: [¹¹C]Cimbi-36 is a recently developed serotonin 2A (5-HT_2A) 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-HT_2A receptor antagonist [¹⁸F]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 [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. Results: Test-retest variability of [¹¹C]Cimbi-36 non-displaceable binding potential (BP_ND) 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 BP_NDs 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. Conclusions: Excellent test-retest reproducibility highlights the potential of [¹¹C]Cimbi-36 for PET imaging of 5-HT_2A receptor agonist binding in vivo. Our data suggest that Cimbi-36 and altanserin both bind to 5-HT_2A receptors, but in regions with high 5-HT_2C receptor density, choroid plexus and hippocampus, the [¹¹C]Cimbi-36 binding likely represents binding to both 5-HT_2A and 5-HT_2C receptors.

Original language	English
Journal	NeuroImage
Volume	130
Pages (from-to)	167-74
Number of pages	8
ISSN	1053-8119
DOIs	https://doi.org/10.1016/j.neuroimage.2016.02.001
Publication status	Published - 15 Apr 2016

Keywords

Journal Article
Research Support, Non-U.S. Gov't

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10.1016/j.neuroimage.2016.02.001

Cite this

Ettrup, A., Svarer, C., McMahon, B., da Cunha-Bang, S., Lehel, S., Møller, K., Dyssegaard, A., Ganz, M., Beliveau, V., Jørgensen, L. M., Gillings, N., & Knudsen, G. M. (2016). 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. NeuroImage, 130, 167-74. https://doi.org/10.1016/j.neuroimage.2016.02.001

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, GM 2016, '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', NeuroImage, vol. 130, pp. 167-74. https://doi.org/10.1016/j.neuroimage.2016.02.001

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title = "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",

abstract = "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. 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 [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. Results: 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. Conclusions: 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.",

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author = "Anders Ettrup and Claus Svarer and Brenda McMahon and {da Cunha-Bang}, Sofi and Szabolcs Lehel and Kirsten M{\o}ller and Agnete Dyssegaard and Melanie Ganz and Vincent Beliveau and J{\o}rgensen, {Louise M{\o}ller} and Nic Gillings and Knudsen, {Gitte Moos}",

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doi = "10.1016/j.neuroimage.2016.02.001",

language = "English",

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pages = "167--74",

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TY - JOUR

T1 - Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36

T2 - Test-retest reproducibility and head-to-head comparison with the antagonist [18F]altanserin

AU - Ettrup, Anders

AU - Svarer, Claus

AU - McMahon, Brenda

AU - da Cunha-Bang, Sofi

AU - Lehel, Szabolcs

AU - Møller, Kirsten

AU - Dyssegaard, Agnete

AU - Ganz, Melanie

AU - Beliveau, Vincent

AU - Jørgensen, Louise Møller

AU - Gillings, Nic

AU - Knudsen, Gitte Moos

PY - 2016/4/15

Y1 - 2016/4/15

N2 - 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. 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 [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. Results: 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. Conclusions: 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.

AB - 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. 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 [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. Results: 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. Conclusions: 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.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.neuroimage.2016.02.001

DO - 10.1016/j.neuroimage.2016.02.001

M3 - Journal article

C2 - 26876490

SN - 1053-8119

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JO - NeuroImage

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