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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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Detalles Bibliográficos
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
Descripción
Sumario: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.