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In vivo vesicular acetylcholine transporter density in human peripheral organs: an [(18)F]FEOBV PET/CT study

BACKGROUND: The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson’s disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [(18)F]FEOBV PET, we here...

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Autores principales: Horsager, Jacob, Okkels, Niels, Van Den Berge, Nathalie, Jacobsen, Jan, Schact, Anna, Munk, Ole Lajord, Vang, Kim, Bender, Dirk, Brooks, David J., Borghammer, Per
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975951/
https://www.ncbi.nlm.nih.gov/pubmed/35362761
http://dx.doi.org/10.1186/s13550-022-00889-9
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author Horsager, Jacob
Okkels, Niels
Van Den Berge, Nathalie
Jacobsen, Jan
Schact, Anna
Munk, Ole Lajord
Vang, Kim
Bender, Dirk
Brooks, David J.
Borghammer, Per
author_facet Horsager, Jacob
Okkels, Niels
Van Den Berge, Nathalie
Jacobsen, Jan
Schact, Anna
Munk, Ole Lajord
Vang, Kim
Bender, Dirk
Brooks, David J.
Borghammer, Per
author_sort Horsager, Jacob
collection PubMed
description BACKGROUND: The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson’s disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [(18)F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects. We included 15 healthy subjects aged 53–86 years for 70 min dynamic PET protocol of peripheral organs. We performed kinetic modelling of the adrenal gland, pancreas, myocardium, renal cortex, spleen, colon, and muscle using an image-derived input function from the aorta. A metabolite correction model was generated from venous blood samples. Three non-linear compartment models were tested. Additional time-activity curves from 6 to 70 min post injection were generated for prostate, thyroid, submandibular-, parotid-, and lacrimal glands. RESULTS: A one-tissue compartment model generated the most robust fits to the data. Total volume-of-distribution rank order was: adrenal gland > pancreas > myocardium > spleen > renal cortex > muscle > colon. We found significant linear correlations between total volumes-of-distribution and standard uptake values in most organs. CONCLUSION: High [(18)F]FEOBV PET signal was found in structures with known cholinergic activity. We conclude that [(18)F]FEOBV PET is a valid tool for estimating VAChT density in human peripheral organs. Simple static images may replace kinetic modeling in some organs and significantly shorten scan duration. Clinical Trial Registration Trial registration: NCT, NCT03554551. Registered 31 May 2018. https://clinicaltrials.gov/ct2/show/NCT03554551?term=NCT03554551&draw=2&rank=1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-022-00889-9.
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spelling pubmed-89759512022-04-20 In vivo vesicular acetylcholine transporter density in human peripheral organs: an [(18)F]FEOBV PET/CT study Horsager, Jacob Okkels, Niels Van Den Berge, Nathalie Jacobsen, Jan Schact, Anna Munk, Ole Lajord Vang, Kim Bender, Dirk Brooks, David J. Borghammer, Per EJNMMI Res Original Research BACKGROUND: The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson’s disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [(18)F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects. We included 15 healthy subjects aged 53–86 years for 70 min dynamic PET protocol of peripheral organs. We performed kinetic modelling of the adrenal gland, pancreas, myocardium, renal cortex, spleen, colon, and muscle using an image-derived input function from the aorta. A metabolite correction model was generated from venous blood samples. Three non-linear compartment models were tested. Additional time-activity curves from 6 to 70 min post injection were generated for prostate, thyroid, submandibular-, parotid-, and lacrimal glands. RESULTS: A one-tissue compartment model generated the most robust fits to the data. Total volume-of-distribution rank order was: adrenal gland > pancreas > myocardium > spleen > renal cortex > muscle > colon. We found significant linear correlations between total volumes-of-distribution and standard uptake values in most organs. CONCLUSION: High [(18)F]FEOBV PET signal was found in structures with known cholinergic activity. We conclude that [(18)F]FEOBV PET is a valid tool for estimating VAChT density in human peripheral organs. Simple static images may replace kinetic modeling in some organs and significantly shorten scan duration. Clinical Trial Registration Trial registration: NCT, NCT03554551. Registered 31 May 2018. https://clinicaltrials.gov/ct2/show/NCT03554551?term=NCT03554551&draw=2&rank=1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-022-00889-9. Springer Berlin Heidelberg 2022-04-01 /pmc/articles/PMC8975951/ /pubmed/35362761 http://dx.doi.org/10.1186/s13550-022-00889-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Research
Horsager, Jacob
Okkels, Niels
Van Den Berge, Nathalie
Jacobsen, Jan
Schact, Anna
Munk, Ole Lajord
Vang, Kim
Bender, Dirk
Brooks, David J.
Borghammer, Per
In vivo vesicular acetylcholine transporter density in human peripheral organs: an [(18)F]FEOBV PET/CT study
title In vivo vesicular acetylcholine transporter density in human peripheral organs: an [(18)F]FEOBV PET/CT study
title_full In vivo vesicular acetylcholine transporter density in human peripheral organs: an [(18)F]FEOBV PET/CT study
title_fullStr In vivo vesicular acetylcholine transporter density in human peripheral organs: an [(18)F]FEOBV PET/CT study
title_full_unstemmed In vivo vesicular acetylcholine transporter density in human peripheral organs: an [(18)F]FEOBV PET/CT study
title_short In vivo vesicular acetylcholine transporter density in human peripheral organs: an [(18)F]FEOBV PET/CT study
title_sort in vivo vesicular acetylcholine transporter density in human peripheral organs: an [(18)f]feobv pet/ct study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975951/
https://www.ncbi.nlm.nih.gov/pubmed/35362761
http://dx.doi.org/10.1186/s13550-022-00889-9
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