[ 18 F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease.
Robert K DootAnthony J YoungIlya M NasrallahReagan R WetherillAndrew SiderowfRobert H MachJacob G DubroffPublished in: Cells (2022)
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.
Keyphrases
- nitric oxide synthase
- pet imaging
- positron emission tomography
- oxidative stress
- nitric oxide
- end stage renal disease
- computed tomography
- cerebral ischemia
- early stage
- ejection fraction
- traumatic brain injury
- lipopolysaccharide induced
- chronic kidney disease
- high resolution
- newly diagnosed
- cognitive impairment
- pet ct
- inflammatory response
- peritoneal dialysis
- white matter
- lps induced
- resting state
- prognostic factors
- endothelial cells
- blood brain barrier
- drug delivery
- subarachnoid hemorrhage
- spinal cord injury
- blood pressure
- spinal cord
- radiation therapy
- cancer therapy
- fluorescence imaging
- endoplasmic reticulum stress
- amino acid