Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands

Melanie Ganz; Ling Feng; Hanne Demant Hansen; Vincent Beliveau; Claus Svarer; Gitte Moos Knudsen

doi:10.1177/0271678x16686092

Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands

Melanie Ganz, Ling Feng, Hanne Demant Hansen, Vincent Beliveau, Claus Svarer, Gitte Moos Knudsen

Department of Clinical Medicine

9 Citations (Scopus)

Abstract

In the quantification of positron emission tomography (PET) radiotracer binding, a commonly used method is reference tissue modeling (RTM). RTM necessitates a proper reference and a ubiquitous choice for G-protein coupled receptors is the cerebellum. We investigated regional differences in uptake within the grey matter of the cerebellar hemispheres (CH), the cerebellar white matter (CW), and the cerebellar vermis (CV) for five PET radioligands targeting the serotonin system. Furthermore, we evaluated the impact of choosing different reference regions when quantifying neocortical binding. The PET and MR images are part of the Cimbi database: 5-HT1AR ([11C]CUMI-101, n = 8), 5-HT1BR ([11C]AZ10419369, n = 36), 5-HT2AR ([11C]Cimbi-36, n = 29), 5-HT4R ([11C]SB207145, n = 59), and 5-HTT ([11C]DASB, n = 100). We employed SUIT and FreeSurfer to delineate CV, CW, and CH and quantified mean standardized uptake values (SUV) and nondisplaceable neocortical binding potential (BPND). Statistical difference was assessed with paired nonparametric two-sided Wilcoxon signed-rank tests and multiple comparison corrected via false discovery rate. We demonstrate significant radioligand specific regional differences in cerebellar uptake. These differences persist when using different cerebellar regions for RTM, but the influence on the neocortical BPND is small. Nevertheless, our data highlight the importance of validating each radioligand carefully for defining the optimal reference region.

Original language	English
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	37
Issue number	9
ISSN	0271-678X
DOIs	https://doi.org/10.1177/0271678x16686092
Publication status	Published - 1 Sept 2017

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title = "Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands",

abstract = "In the quantification of positron emission tomography (PET) radiotracer binding, a commonly used method is reference tissue modeling (RTM). RTM necessitates a proper reference and a ubiquitous choice for G-protein coupled receptors is the cerebellum. We investigated regional differences in uptake within the grey matter of the cerebellar hemispheres (CH), the cerebellar white matter (CW), and the cerebellar vermis (CV) for five PET radioligands targeting the serotonin system. Furthermore, we evaluated the impact of choosing different reference regions when quantifying neocortical binding. The PET and MR images are part of the Cimbi database: 5-HT1AR ([11C]CUMI-101, n = 8), 5-HT1BR ([11C]AZ10419369, n = 36), 5-HT2AR ([11C]Cimbi-36, n = 29), 5-HT4R ([11C]SB207145, n = 59), and 5-HTT ([11C]DASB, n = 100). We employed SUIT and FreeSurfer to delineate CV, CW, and CH and quantified mean standardized uptake values (SUV) and nondisplaceable neocortical binding potential (BPND). Statistical difference was assessed with paired nonparametric two-sided Wilcoxon signed-rank tests and multiple comparison corrected via false discovery rate. We demonstrate significant radioligand specific regional differences in cerebellar uptake. These differences persist when using different cerebellar regions for RTM, but the influence on the neocortical BPND is small. Nevertheless, our data highlight the importance of validating each radioligand carefully for defining the optimal reference region.",

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T1 - Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands

AU - Ganz, Melanie

AU - Feng, Ling

AU - Hansen, Hanne Demant

AU - Beliveau, Vincent

AU - Svarer, Claus

AU - Knudsen, Gitte Moos

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N2 - In the quantification of positron emission tomography (PET) radiotracer binding, a commonly used method is reference tissue modeling (RTM). RTM necessitates a proper reference and a ubiquitous choice for G-protein coupled receptors is the cerebellum. We investigated regional differences in uptake within the grey matter of the cerebellar hemispheres (CH), the cerebellar white matter (CW), and the cerebellar vermis (CV) for five PET radioligands targeting the serotonin system. Furthermore, we evaluated the impact of choosing different reference regions when quantifying neocortical binding. The PET and MR images are part of the Cimbi database: 5-HT1AR ([11C]CUMI-101, n = 8), 5-HT1BR ([11C]AZ10419369, n = 36), 5-HT2AR ([11C]Cimbi-36, n = 29), 5-HT4R ([11C]SB207145, n = 59), and 5-HTT ([11C]DASB, n = 100). We employed SUIT and FreeSurfer to delineate CV, CW, and CH and quantified mean standardized uptake values (SUV) and nondisplaceable neocortical binding potential (BPND). Statistical difference was assessed with paired nonparametric two-sided Wilcoxon signed-rank tests and multiple comparison corrected via false discovery rate. We demonstrate significant radioligand specific regional differences in cerebellar uptake. These differences persist when using different cerebellar regions for RTM, but the influence on the neocortical BPND is small. Nevertheless, our data highlight the importance of validating each radioligand carefully for defining the optimal reference region.

AB - In the quantification of positron emission tomography (PET) radiotracer binding, a commonly used method is reference tissue modeling (RTM). RTM necessitates a proper reference and a ubiquitous choice for G-protein coupled receptors is the cerebellum. We investigated regional differences in uptake within the grey matter of the cerebellar hemispheres (CH), the cerebellar white matter (CW), and the cerebellar vermis (CV) for five PET radioligands targeting the serotonin system. Furthermore, we evaluated the impact of choosing different reference regions when quantifying neocortical binding. The PET and MR images are part of the Cimbi database: 5-HT1AR ([11C]CUMI-101, n = 8), 5-HT1BR ([11C]AZ10419369, n = 36), 5-HT2AR ([11C]Cimbi-36, n = 29), 5-HT4R ([11C]SB207145, n = 59), and 5-HTT ([11C]DASB, n = 100). We employed SUIT and FreeSurfer to delineate CV, CW, and CH and quantified mean standardized uptake values (SUV) and nondisplaceable neocortical binding potential (BPND). Statistical difference was assessed with paired nonparametric two-sided Wilcoxon signed-rank tests and multiple comparison corrected via false discovery rate. We demonstrate significant radioligand specific regional differences in cerebellar uptake. These differences persist when using different cerebellar regions for RTM, but the influence on the neocortical BPND is small. Nevertheless, our data highlight the importance of validating each radioligand carefully for defining the optimal reference region.

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DO - 10.1177/0271678x16686092

M3 - Journal article

C2 - 28075185

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VL - 37

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 9

ER -

Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands

Abstract

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