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Characterization of [11C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain

Purpose [ 11 C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [ 11 C]Lu AE92686 has high affinity for PDE10A ( IC 50  = 0.39 nM) and may also be suitable for examination of the substa... Full description

Journal Title: European Journal of Nuclear Medicine and Molecular Imaging 2016, Vol.44 (2), p.308-320
Main Author: Yang, Kai-Chun
Other Authors: Stepanov, Vladimir , Amini, Nahid , Martinsson, Stefan , Takano, Akihiro , Nielsen, Jacob , Bundgaard, Christoffer , Bang-Andersen, Benny , Grimwood, Sarah , Halldin, Christer , Farde, Lars , Finnema, Sjoerd J
Format: Electronic Article Electronic Article
Language: English
Subjects:
PET
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 1619-7070
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title: Characterization of [11C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain
format: Article
creator:
  • Yang, Kai-Chun
  • Stepanov, Vladimir
  • Amini, Nahid
  • Martinsson, Stefan
  • Takano, Akihiro
  • Nielsen, Jacob
  • Bundgaard, Christoffer
  • Bang-Andersen, Benny
  • Grimwood, Sarah
  • Halldin, Christer
  • Farde, Lars
  • Finnema, Sjoerd J
subjects:
  • [11C]Lu AE92686
  • Animals
  • Brain
  • Brain - diagnostic imaging
  • Brain - metabolism
  • Cardiology
  • Female
  • Humans
  • Imaging
  • Isotope Labeling - methods
  • Ligands
  • Lu AE92686
  • Macaca fascicularis
  • Medicin och hälsovetenskap
  • Medicine
  • Medicine & Public Health
  • Metabolic Clearance Rate
  • Molecular Imaging - methods
  • Monkey
  • Monkeys & apes
  • MP-10
  • Nuclear Medicine
  • Oncology
  • Organ Specificity
  • Original
  • Original Article
  • Orthopedics
  • PET
  • Phosphodiesterase 10A
  • Phosphodiesterase Inhibitors - pharmacokinetics
  • Phosphoric Diester Hydrolases - metabolism
  • Positron-Emission Tomography - methods
  • Pyridines - pharmacokinetics
  • Radiology
  • Radiology Nuclear Medicine
  • Radiopharmaceuticals - pharmacokinetics
  • Substantia nigra
  • Tissue Distribution
  • Tomography
  • Triazoles - pharmacokinetics
ispartof: European Journal of Nuclear Medicine and Molecular Imaging, 2016, Vol.44 (2), p.308-320
description: Purpose [ 11 C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [ 11 C]Lu AE92686 has high affinity for PDE10A ( IC 50  = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional [ 11 C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. Methods A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). [ 11 C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Results Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume ( V T ) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V T values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V T values increased by ∼30 % with increasing PET measurement duration from 63 to 123 min, while V T values in target regions remained stable. Both pretreatment drugs significantly decreased [ 11 C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential ( BP ND ) values, derived with the simplified reference tissue model (SRTM), were 13–17 in putamen and 3–5 in substantia nigra and correlated well to values from the Logan plot analysis. Conclusions The method proposed for quantification of [ 11 C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [ 11 C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia nigra.
language: eng
source:
identifier: ISSN: 1619-7070
fulltext: no_fulltext
issn:
  • 1619-7070
  • 1619-7089
  • 1619-7089
url: Link


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titleCharacterization of [11C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain
creatorYang, Kai-Chun ; Stepanov, Vladimir ; Amini, Nahid ; Martinsson, Stefan ; Takano, Akihiro ; Nielsen, Jacob ; Bundgaard, Christoffer ; Bang-Andersen, Benny ; Grimwood, Sarah ; Halldin, Christer ; Farde, Lars ; Finnema, Sjoerd J
creatorcontribYang, Kai-Chun ; Stepanov, Vladimir ; Amini, Nahid ; Martinsson, Stefan ; Takano, Akihiro ; Nielsen, Jacob ; Bundgaard, Christoffer ; Bang-Andersen, Benny ; Grimwood, Sarah ; Halldin, Christer ; Farde, Lars ; Finnema, Sjoerd J
descriptionPurpose [ 11 C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [ 11 C]Lu AE92686 has high affinity for PDE10A ( IC 50  = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional [ 11 C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. Methods A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). [ 11 C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Results Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume ( V T ) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V T values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V T values increased by ∼30 % with increasing PET measurement duration from 63 to 123 min, while V T values in target regions remained stable. Both pretreatment drugs significantly decreased [ 11 C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential ( BP ND ) values, derived with the simplified reference tissue model (SRTM), were 13–17 in putamen and 3–5 in substantia nigra and correlated well to values from the Logan plot analysis. Conclusions The method proposed for quantification of [ 11 C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [ 11 C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia nigra.
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languageeng
publisherBerlin/Heidelberg: Springer Berlin Heidelberg
subject[11C]Lu AE92686 ; Animals ; Brain ; Brain - diagnostic imaging ; Brain - metabolism ; Cardiology ; Female ; Humans ; Imaging ; Isotope Labeling - methods ; Ligands ; Lu AE92686 ; Macaca fascicularis ; Medicin och hälsovetenskap ; Medicine ; Medicine & Public Health ; Metabolic Clearance Rate ; Molecular Imaging - methods ; Monkey ; Monkeys & apes ; MP-10 ; Nuclear Medicine ; Oncology ; Organ Specificity ; Original ; Original Article ; Orthopedics ; PET ; Phosphodiesterase 10A ; Phosphodiesterase Inhibitors - pharmacokinetics ; Phosphoric Diester Hydrolases - metabolism ; Positron-Emission Tomography - methods ; Pyridines - pharmacokinetics ; Radiology ; Radiology Nuclear Medicine ; Radiopharmaceuticals - pharmacokinetics ; Substantia nigra ; Tissue Distribution ; Tomography ; Triazoles - pharmacokinetics
ispartofEuropean Journal of Nuclear Medicine and Molecular Imaging, 2016, Vol.44 (2), p.308-320
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0Yang, Kai-Chun
1Stepanov, Vladimir
2Amini, Nahid
3Martinsson, Stefan
4Takano, Akihiro
5Nielsen, Jacob
6Bundgaard, Christoffer
7Bang-Andersen, Benny
8Grimwood, Sarah
9Halldin, Christer
10Farde, Lars
11Finnema, Sjoerd J
title
0Characterization of [11C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain
1European Journal of Nuclear Medicine and Molecular Imaging
addtitle
0Eur J Nucl Med Mol Imaging
1Eur J Nucl Med Mol Imaging
descriptionPurpose [ 11 C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [ 11 C]Lu AE92686 has high affinity for PDE10A ( IC 50  = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional [ 11 C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. Methods A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). [ 11 C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Results Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume ( V T ) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V T values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V T values increased by ∼30 % with increasing PET measurement duration from 63 to 123 min, while V T values in target regions remained stable. Both pretreatment drugs significantly decreased [ 11 C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential ( BP ND ) values, derived with the simplified reference tissue model (SRTM), were 13–17 in putamen and 3–5 in substantia nigra and correlated well to values from the Logan plot analysis. Conclusions The method proposed for quantification of [ 11 C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [ 11 C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia nigra.
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1Animals
2Brain
3Brain - diagnostic imaging
4Brain - metabolism
5Cardiology
6Female
7Humans
8Imaging
9Isotope Labeling - methods
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11Lu AE92686
12Macaca fascicularis
13Medicin och hälsovetenskap
14Medicine
15Medicine & Public Health
16Metabolic Clearance Rate
17Molecular Imaging - methods
18Monkey
19Monkeys & apes
20MP-10
21Nuclear Medicine
22Oncology
23Organ Specificity
24Original
25Original Article
26Orthopedics
27PET
28Phosphodiesterase 10A
29Phosphodiesterase Inhibitors - pharmacokinetics
30Phosphoric Diester Hydrolases - metabolism
31Positron-Emission Tomography - methods
32Pyridines - pharmacokinetics
33Radiology
34Radiology Nuclear Medicine
35Radiopharmaceuticals - pharmacokinetics
36Substantia nigra
37Tissue Distribution
38Tomography
39Triazoles - pharmacokinetics
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5Nielsen, Jacob
6Bundgaard, Christoffer
7Bang-Andersen, Benny
8Grimwood, Sarah
9Halldin, Christer
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titleCharacterization of [11C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain
authorYang, Kai-Chun ; Stepanov, Vladimir ; Amini, Nahid ; Martinsson, Stefan ; Takano, Akihiro ; Nielsen, Jacob ; Bundgaard, Christoffer ; Bang-Andersen, Benny ; Grimwood, Sarah ; Halldin, Christer ; Farde, Lars ; Finnema, Sjoerd J
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0[11C]Lu AE92686
1Animals
2Brain
3Brain - diagnostic imaging
4Brain - metabolism
5Cardiology
6Female
7Humans
8Imaging
9Isotope Labeling - methods
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12Macaca fascicularis
13Medicin och hälsovetenskap
14Medicine
15Medicine & Public Health
16Metabolic Clearance Rate
17Molecular Imaging - methods
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19Monkeys & apes
20MP-10
21Nuclear Medicine
22Oncology
23Organ Specificity
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25Original Article
26Orthopedics
27PET
28Phosphodiesterase 10A
29Phosphodiesterase Inhibitors - pharmacokinetics
30Phosphoric Diester Hydrolases - metabolism
31Positron-Emission Tomography - methods
32Pyridines - pharmacokinetics
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34Radiology Nuclear Medicine
35Radiopharmaceuticals - pharmacokinetics
36Substantia nigra
37Tissue Distribution
38Tomography
39Triazoles - pharmacokinetics
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1Stepanov, Vladimir
2Amini, Nahid
3Martinsson, Stefan
4Takano, Akihiro
5Nielsen, Jacob
6Bundgaard, Christoffer
7Bang-Andersen, Benny
8Grimwood, Sarah
9Halldin, Christer
10Farde, Lars
11Finnema, Sjoerd J
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0Yang, Kai-Chun
1Stepanov, Vladimir
2Amini, Nahid
3Martinsson, Stefan
4Takano, Akihiro
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7Bang-Andersen, Benny
8Grimwood, Sarah
9Halldin, Christer
10Farde, Lars
11Finnema, Sjoerd J
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atitleCharacterization of [11C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain
jtitleEuropean Journal of Nuclear Medicine and Molecular Imaging
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abstractPurpose [ 11 C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [ 11 C]Lu AE92686 has high affinity for PDE10A ( IC 50  = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional [ 11 C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. Methods A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). [ 11 C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Results Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume ( V T ) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V T values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V T values increased by ∼30 % with increasing PET measurement duration from 63 to 123 min, while V T values in target regions remained stable. Both pretreatment drugs significantly decreased [ 11 C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential ( BP ND ) values, derived with the simplified reference tissue model (SRTM), were 13–17 in putamen and 3–5 in substantia nigra and correlated well to values from the Logan plot analysis. Conclusions The method proposed for quantification of [ 11 C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [ 11 C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia nigra.
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pmid27817159
doi10.1007/s00259-016-3544-9
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