Cerebral 5-HT release correlates with [C-11]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Cerebral 5-HT release correlates with [C-11]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain. / Jørgensen, Louise M; Weikop, Pia; Villadsen, Jonas; Visnapuu, Tanel; Ettrup, Anders; Hansen, Hanne D.; Baandrup, Anders O.; Andersen, Flemming L.; Bjarkam, Carsten R.; Thomsen, Carsten; Jespersen, Bo; Knudsen, Gitte M.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 37, No. 2, 02.2017, p. 425-434.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Jørgensen, LM, Weikop, P, Villadsen, J, Visnapuu, T, Ettrup, A, Hansen, HD, Baandrup, AO, Andersen, FL, Bjarkam, CR, Thomsen, C, Jespersen, B & Knudsen, GM 2017, 'Cerebral 5-HT release correlates with [C-11]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain', Journal of Cerebral Blood Flow and Metabolism, vol. 37, no. 2, pp. 425-434. https://doi.org/10.1177/0271678X16629483

APA

Jørgensen, L. M., Weikop, P., Villadsen, J., Visnapuu, T., Ettrup, A., Hansen, H. D., Baandrup, A. O., Andersen, F. L., Bjarkam, C. R., Thomsen, C., Jespersen, B., & Knudsen, G. M. (2017). Cerebral 5-HT release correlates with [C-11]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain. Journal of Cerebral Blood Flow and Metabolism, 37(2), 425-434. https://doi.org/10.1177/0271678X16629483

Vancouver

Jørgensen LM, Weikop P, Villadsen J, Visnapuu T, Ettrup A, Hansen HD et al. Cerebral 5-HT release correlates with [C-11]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain. Journal of Cerebral Blood Flow and Metabolism. 2017 Feb;37(2):425-434. https://doi.org/10.1177/0271678X16629483

Author

Jørgensen, Louise M ; Weikop, Pia ; Villadsen, Jonas ; Visnapuu, Tanel ; Ettrup, Anders ; Hansen, Hanne D. ; Baandrup, Anders O. ; Andersen, Flemming L. ; Bjarkam, Carsten R. ; Thomsen, Carsten ; Jespersen, Bo ; Knudsen, Gitte M. / Cerebral 5-HT release correlates with [C-11]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain. In: Journal of Cerebral Blood Flow and Metabolism. 2017 ; Vol. 37, No. 2. pp. 425-434.

Bibtex

@article{9d1b73557e574ff29b761753c18b86b5,
title = "Cerebral 5-HT release correlates with [C-11]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain",
abstract = "Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [11C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [11C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular5-HT levels with microdialysis and [11C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram {\th} pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to depletecerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2–11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5-HT release, and induced a varying degree of decline in[11C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT2A receptor occupancy indicates that [11C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high.",
keywords = "Positron emission tomography, 5-HT, brain imaging, kinetic modelling, neurosurgery",
author = "J{\o}rgensen, {Louise M} and Pia Weikop and Jonas Villadsen and Tanel Visnapuu and Anders Ettrup and Hansen, {Hanne D.} and Baandrup, {Anders O.} and Andersen, {Flemming L.} and Bjarkam, {Carsten R.} and Carsten Thomsen and Bo Jespersen and Knudsen, {Gitte M.}",
year = "2017",
month = feb,
doi = "10.1177/0271678X16629483",
language = "English",
volume = "37",
pages = "425--434",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "SAGE Publications",
number = "2",

}

RIS

TY - JOUR

T1 - Cerebral 5-HT release correlates with [C-11]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain

AU - Jørgensen, Louise M

AU - Weikop, Pia

AU - Villadsen, Jonas

AU - Visnapuu, Tanel

AU - Ettrup, Anders

AU - Hansen, Hanne D.

AU - Baandrup, Anders O.

AU - Andersen, Flemming L.

AU - Bjarkam, Carsten R.

AU - Thomsen, Carsten

AU - Jespersen, Bo

AU - Knudsen, Gitte M.

PY - 2017/2

Y1 - 2017/2

N2 - Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [11C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [11C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular5-HT levels with microdialysis and [11C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram þ pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to depletecerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2–11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5-HT release, and induced a varying degree of decline in[11C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT2A receptor occupancy indicates that [11C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high.

AB - Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [11C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [11C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular5-HT levels with microdialysis and [11C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram þ pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to depletecerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2–11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5-HT release, and induced a varying degree of decline in[11C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT2A receptor occupancy indicates that [11C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high.

KW - Positron emission tomography

KW - 5-HT

KW - brain imaging

KW - kinetic modelling

KW - neurosurgery

U2 - 10.1177/0271678X16629483

DO - 10.1177/0271678X16629483

M3 - Journal article

C2 - 26825776

VL - 37

SP - 425

EP - 434

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 2

ER -

ID: 174664492