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[(18)F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease

Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neurop...

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Autores principales: Doot, Robert K., Young, Anthony J., Nasrallah, Ilya M., Wetherill, Reagan R., Siderowf, Andrew, Mach, Robert H., Dubroff, Jacob G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563966/
https://www.ncbi.nlm.nih.gov/pubmed/36231041
http://dx.doi.org/10.3390/cells11193081
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author Doot, Robert K.
Young, Anthony J.
Nasrallah, Ilya M.
Wetherill, Reagan R.
Siderowf, Andrew
Mach, Robert H.
Dubroff, Jacob G.
author_facet Doot, Robert K.
Young, Anthony J.
Nasrallah, Ilya M.
Wetherill, Reagan R.
Siderowf, Andrew
Mach, Robert H.
Dubroff, Jacob G.
author_sort Doot, Robert K.
collection PubMed
description Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neuropathophysiological mechanism driving Parkinson’s disease (PD). We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [(18)F]NOS radiotracer to measure neuroinflammation in idiopathic PD. Ten adults consisting of 6 PD patients and 4 healthy controls (HC) underwent one hour of dynamic [(18)F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [(18)F]NOS whole brain distribution volume (V(T)) in PD patients compared to age-matched healthy controls (p < 0.008) via a 1-tissue compartment (TC) model. The rate constant K1 for transport from blood into tissue did not differ between groups (p = 0.72). These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD and indicate that [(18)F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation.
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spelling pubmed-95639662022-10-15 [(18)F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease Doot, Robert K. Young, Anthony J. Nasrallah, Ilya M. Wetherill, Reagan R. Siderowf, Andrew Mach, Robert H. Dubroff, Jacob G. Cells Article Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neuropathophysiological mechanism driving Parkinson’s disease (PD). We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [(18)F]NOS radiotracer to measure neuroinflammation in idiopathic PD. Ten adults consisting of 6 PD patients and 4 healthy controls (HC) underwent one hour of dynamic [(18)F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [(18)F]NOS whole brain distribution volume (V(T)) in PD patients compared to age-matched healthy controls (p < 0.008) via a 1-tissue compartment (TC) model. The rate constant K1 for transport from blood into tissue did not differ between groups (p = 0.72). These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD and indicate that [(18)F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation. MDPI 2022-09-30 /pmc/articles/PMC9563966/ /pubmed/36231041 http://dx.doi.org/10.3390/cells11193081 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Doot, Robert K.
Young, Anthony J.
Nasrallah, Ilya M.
Wetherill, Reagan R.
Siderowf, Andrew
Mach, Robert H.
Dubroff, Jacob G.
[(18)F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease
title [(18)F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease
title_full [(18)F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease
title_fullStr [(18)F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease
title_full_unstemmed [(18)F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease
title_short [(18)F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease
title_sort [(18)f]nos pet brain imaging suggests elevated neuroinflammation in idiopathic parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563966/
https://www.ncbi.nlm.nih.gov/pubmed/36231041
http://dx.doi.org/10.3390/cells11193081
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