18F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease.

Robert K Doot, Anthony J Young, Ilya M Nasrallah, Reagan R Wetherill, Andrew Siderowf, Robert H Mach, Jacob G Dubroff

Cells 2022 Sep 30

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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 [18F]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 [18F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [18F]NOS whole brain distribution volume (VT) 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 [18F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation.

Citation

Robert K Doot, Anthony J Young, Ilya M Nasrallah, Reagan R Wetherill, Andrew Siderowf, Robert H Mach, Jacob G Dubroff. 18F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease. Cells. 2022 Sep 30;11(19)