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

Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningfagfællebedømt

Standard

Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36: test-retest reproducibility and comparison with [18F]altanserin. / Ettrup, Anders; Svarer, Claus; McMahon, Brenda; da Cunha-Bang, S.; Lehel, S; Møller, K; Dyssegaard, Agnete; Ganz, Melanie; Beliveau, Vincent; Jørgensen, Louise Møller; Gillings, N; Knudsen, Gitte Moos.

2015. Abstract fra European Congress on Neuropharmacology, Amsterdam, Holland.

Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningfagfællebedømt

Harvard

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 2015, 'Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36: test-retest reproducibility and comparison with [18F]altanserin', European Congress on Neuropharmacology, Amsterdam, Holland, 29/08/2015 - 01/09/2015.

APA

Ettrup, A., Svarer, C., McMahon, B., da Cunha-Bang, S., Lehel, S., Møller, K., ... Knudsen, G. M. (2015). Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36: test-retest reproducibility and comparison with [18F]altanserin. Abstract fra European Congress on Neuropharmacology, Amsterdam, Holland.

Vancouver

Ettrup A, Svarer C, McMahon B, da Cunha-Bang S, Lehel S, Møller K o.a.. Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36: test-retest reproducibility and comparison with [18F]altanserin. 2015. Abstract fra European Congress on Neuropharmacology, Amsterdam, Holland.

Author

Ettrup, Anders ; Svarer, Claus ; McMahon, Brenda ; da Cunha-Bang, S. ; Lehel, S ; Møller, K ; Dyssegaard, Agnete ; Ganz, Melanie ; Beliveau, Vincent ; Jørgensen, Louise Møller ; Gillings, N ; Knudsen, Gitte Moos. / Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36: test-retest reproducibility and comparison with [18F]altanserin. Abstract fra European Congress on Neuropharmacology, Amsterdam, Holland.

Bibtex

@conference{5d8695bdb9194ca7ac226335aea0a459,
title = "Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36: test-retest reproducibility and comparison with [18F]altanserin",
abstract = "Objectives: Serotonin 2A (5-HT2A) receptor agonist binding measured with positron emission tomography (PET) may be clinically and pathophysiologically relevant and may reflect endogenous 5-HT levels in vivo. Here, we assess test-retest variability of the newly developed 5-HT2A receptor agonist PET radioligand [11C]Cimbi-36 [1] and compare brain distribution to the 5-HT2A receptor antagonist [18F]altanserin. Methods: Sixteen healthy volunteers were included in the study (mean age: 23.9±6.4 years, 6 males). All subjects were PET scanned for 120 minutes after a bolus injection with [11C]Cimbi-36. Eight subjects were re-scanned with [11C]Cimbi-36 (mean time ±SD between PET scans: 31±16 days) while other 8 subjects were PET scanned for 40 minutes with [18F]altanserin after a bolus plus constant infusion (Kbol=1.75 hours, mean time ±SD between PET scans: 133±88 days). Binding potentials (BP) were quantified with cerebellum as reference region for both radioligands. The regional non-displaceable BP (BPND) of [11C]Cimbi-36 were assessed with distribution volumes from a 2-tissue compartment model (2TCM) based on arterial input measurements and with reference tissue models, while the BP's for [18F]altanserin were assessed by radioactivities in specific brain regions and plasma assuming steady-state conditions of the radioligand. Results: The absolute differences from test to retest in [11C]Cimbi-36 BPND derived from reference tissue models in high-binding cortical regions were consistently less than 5{\%}, indicating a higher test-retest reproducibility in measures of [11C]Cimbi-36 binding in the human brain compared to previous results with [18F]altanserin [2]. As expected, test-retest variability was slightly higher for BPND measures derived from 2TCM and in smaller brain regions. We found a highly significant correlation between regional BPNDs of [11C]Cimbi-36 and [18F]altanserin with-in subjects (mean Pearsons's r-value: 0.95±0.04) suggesting a similar regional binding of the radioligands. The highly significant correlation remained when pooling regional BPNDs from all subjects (Pearson's r=0.92, p<0.0001) and no regionally specific deviations from the correlation between the two radioligands were observed. Voxel-based analyses of mean standardized [11C]Cimbi-36 and [18F]altanserin BPND images showed that binding of [18F]altanserin relative to [11C]Cimbi-36 was higher in regions corresponding to gray matter in cerebral cortex, but lower in the white matter and in a region corresponding to the choroid plexus. Conclusions: Good reproducibility in the human brain, particular in the cortical areas, highlights the potential of [11C]Cimbi-36 as a PET radioligand in longitudinal studies assessing 5-HT2A receptor agonist binding and in studies to measure changes in binding due to fluctuations in the levels of 5-HT. [11C]Cimbi-36 and [18F]altanserin both bind with high affinity to 5-HT2A receptors, but [11C]Cimbi-36 has greater relative selectivity for 5-HT2C receptors as compared to [18F]altanserin, which is the likely explanation for the higher binding of [11C]Cimbi-36 in choroid plexus. Our results do not suggest any regional differences in binding to high-affinity versus low-affinity states of 5-HT2A receptors. References [1] Ettrup, A., da Cunha-Bang, S., McMahon, B., Lehel, S., Dyssegaard, A., et al., 2014. J. Cereb. Blood Flow Metab 34, 1188–96 [2] Haugbol, S., Pinborg, L.H., Arfan, H.M., Frokjaer., V.M., Madsen J., et al., 2007. Eur. J. Nucl. Med. Mol. Imaging 34, 910–5",
author = "Anders Ettrup and Claus Svarer and Brenda McMahon and {da Cunha-Bang}, S. and S Lehel and K M{\o}ller and Agnete Dyssegaard and Melanie Ganz and Vincent Beliveau and J{\o}rgensen, {Louise M{\o}ller} and N Gillings and Knudsen, {Gitte Moos}",
note = "Citation: European Neuropsychopharmacology 2015;25(Suppl 2):S309 ; European Congress on Neuropharmacology ; Conference date: 29-08-2015 Through 01-09-2015",
year = "2015",
language = "English",
url = "https://www.ecnp.eu/about-ecnp/history/past-ecnp-meetings/past-congresses/Amsterdam2015.aspx",

}

RIS

TY - ABST

T1 - Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36: test-retest reproducibility and comparison with [18F]altanserin

AU - Ettrup, Anders

AU - Svarer, Claus

AU - McMahon, Brenda

AU - da Cunha-Bang, S.

AU - Lehel, S

AU - Møller, K

AU - Dyssegaard, Agnete

AU - Ganz, Melanie

AU - Beliveau, Vincent

AU - Jørgensen, Louise Møller

AU - Gillings, N

AU - Knudsen, Gitte Moos

N1 - Citation: European Neuropsychopharmacology 2015;25(Suppl 2):S309

PY - 2015

Y1 - 2015

N2 - Objectives: Serotonin 2A (5-HT2A) receptor agonist binding measured with positron emission tomography (PET) may be clinically and pathophysiologically relevant and may reflect endogenous 5-HT levels in vivo. Here, we assess test-retest variability of the newly developed 5-HT2A receptor agonist PET radioligand [11C]Cimbi-36 [1] and compare brain distribution to the 5-HT2A receptor antagonist [18F]altanserin. Methods: Sixteen healthy volunteers were included in the study (mean age: 23.9±6.4 years, 6 males). All subjects were PET scanned for 120 minutes after a bolus injection with [11C]Cimbi-36. Eight subjects were re-scanned with [11C]Cimbi-36 (mean time ±SD between PET scans: 31±16 days) while other 8 subjects were PET scanned for 40 minutes with [18F]altanserin after a bolus plus constant infusion (Kbol=1.75 hours, mean time ±SD between PET scans: 133±88 days). Binding potentials (BP) were quantified with cerebellum as reference region for both radioligands. The regional non-displaceable BP (BPND) of [11C]Cimbi-36 were assessed with distribution volumes from a 2-tissue compartment model (2TCM) based on arterial input measurements and with reference tissue models, while the BP's for [18F]altanserin were assessed by radioactivities in specific brain regions and plasma assuming steady-state conditions of the radioligand. Results: The absolute differences from test to retest in [11C]Cimbi-36 BPND derived from reference tissue models in high-binding cortical regions were consistently less than 5%, indicating a higher test-retest reproducibility in measures of [11C]Cimbi-36 binding in the human brain compared to previous results with [18F]altanserin [2]. As expected, test-retest variability was slightly higher for BPND measures derived from 2TCM and in smaller brain regions. We found a highly significant correlation between regional BPNDs of [11C]Cimbi-36 and [18F]altanserin with-in subjects (mean Pearsons's r-value: 0.95±0.04) suggesting a similar regional binding of the radioligands. The highly significant correlation remained when pooling regional BPNDs from all subjects (Pearson's r=0.92, p<0.0001) and no regionally specific deviations from the correlation between the two radioligands were observed. Voxel-based analyses of mean standardized [11C]Cimbi-36 and [18F]altanserin BPND images showed that binding of [18F]altanserin relative to [11C]Cimbi-36 was higher in regions corresponding to gray matter in cerebral cortex, but lower in the white matter and in a region corresponding to the choroid plexus. Conclusions: Good reproducibility in the human brain, particular in the cortical areas, highlights the potential of [11C]Cimbi-36 as a PET radioligand in longitudinal studies assessing 5-HT2A receptor agonist binding and in studies to measure changes in binding due to fluctuations in the levels of 5-HT. [11C]Cimbi-36 and [18F]altanserin both bind with high affinity to 5-HT2A receptors, but [11C]Cimbi-36 has greater relative selectivity for 5-HT2C receptors as compared to [18F]altanserin, which is the likely explanation for the higher binding of [11C]Cimbi-36 in choroid plexus. Our results do not suggest any regional differences in binding to high-affinity versus low-affinity states of 5-HT2A receptors. References [1] Ettrup, A., da Cunha-Bang, S., McMahon, B., Lehel, S., Dyssegaard, A., et al., 2014. J. Cereb. Blood Flow Metab 34, 1188–96 [2] Haugbol, S., Pinborg, L.H., Arfan, H.M., Frokjaer., V.M., Madsen J., et al., 2007. Eur. J. Nucl. Med. Mol. Imaging 34, 910–5

AB - Objectives: Serotonin 2A (5-HT2A) receptor agonist binding measured with positron emission tomography (PET) may be clinically and pathophysiologically relevant and may reflect endogenous 5-HT levels in vivo. Here, we assess test-retest variability of the newly developed 5-HT2A receptor agonist PET radioligand [11C]Cimbi-36 [1] and compare brain distribution to the 5-HT2A receptor antagonist [18F]altanserin. Methods: Sixteen healthy volunteers were included in the study (mean age: 23.9±6.4 years, 6 males). All subjects were PET scanned for 120 minutes after a bolus injection with [11C]Cimbi-36. Eight subjects were re-scanned with [11C]Cimbi-36 (mean time ±SD between PET scans: 31±16 days) while other 8 subjects were PET scanned for 40 minutes with [18F]altanserin after a bolus plus constant infusion (Kbol=1.75 hours, mean time ±SD between PET scans: 133±88 days). Binding potentials (BP) were quantified with cerebellum as reference region for both radioligands. The regional non-displaceable BP (BPND) of [11C]Cimbi-36 were assessed with distribution volumes from a 2-tissue compartment model (2TCM) based on arterial input measurements and with reference tissue models, while the BP's for [18F]altanserin were assessed by radioactivities in specific brain regions and plasma assuming steady-state conditions of the radioligand. Results: The absolute differences from test to retest in [11C]Cimbi-36 BPND derived from reference tissue models in high-binding cortical regions were consistently less than 5%, indicating a higher test-retest reproducibility in measures of [11C]Cimbi-36 binding in the human brain compared to previous results with [18F]altanserin [2]. As expected, test-retest variability was slightly higher for BPND measures derived from 2TCM and in smaller brain regions. We found a highly significant correlation between regional BPNDs of [11C]Cimbi-36 and [18F]altanserin with-in subjects (mean Pearsons's r-value: 0.95±0.04) suggesting a similar regional binding of the radioligands. The highly significant correlation remained when pooling regional BPNDs from all subjects (Pearson's r=0.92, p<0.0001) and no regionally specific deviations from the correlation between the two radioligands were observed. Voxel-based analyses of mean standardized [11C]Cimbi-36 and [18F]altanserin BPND images showed that binding of [18F]altanserin relative to [11C]Cimbi-36 was higher in regions corresponding to gray matter in cerebral cortex, but lower in the white matter and in a region corresponding to the choroid plexus. Conclusions: Good reproducibility in the human brain, particular in the cortical areas, highlights the potential of [11C]Cimbi-36 as a PET radioligand in longitudinal studies assessing 5-HT2A receptor agonist binding and in studies to measure changes in binding due to fluctuations in the levels of 5-HT. [11C]Cimbi-36 and [18F]altanserin both bind with high affinity to 5-HT2A receptors, but [11C]Cimbi-36 has greater relative selectivity for 5-HT2C receptors as compared to [18F]altanserin, which is the likely explanation for the higher binding of [11C]Cimbi-36 in choroid plexus. Our results do not suggest any regional differences in binding to high-affinity versus low-affinity states of 5-HT2A receptors. References [1] Ettrup, A., da Cunha-Bang, S., McMahon, B., Lehel, S., Dyssegaard, A., et al., 2014. J. Cereb. Blood Flow Metab 34, 1188–96 [2] Haugbol, S., Pinborg, L.H., Arfan, H.M., Frokjaer., V.M., Madsen J., et al., 2007. Eur. J. Nucl. Med. Mol. Imaging 34, 910–5

M3 - Conference abstract for conference

T2 - European Congress on Neuropharmacology

Y2 - 29 August 2015 through 1 September 2015

ER -

ID: 186778974