First-in-human neuroimaging of soluble epoxide hydrolase using [18F]FNDP PET
- 13 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in European Journal of Nuclear Medicine and Molecular Imaging
- Vol. 48 (10), 3122-3128
- https://doi.org/10.1007/s00259-021-05231-4
Abstract
Purpose Soluble epoxide hydrolase (sEH) is an enzyme with putative effect on neuroinflammation through its influence on the homeostasis of polyunsaturated fatty acids and related byproducts. sEH is an enzyme that metabolizes anti-inflammatory epoxy fatty acids to the corresponding, relatively inert 1,2-diols. A high availability or activity of sEH promotes vasoconstriction and inflammation in local tissues that may be linked to neuropsychiatric diseases. We developed [18F]FNDP to study sEH in vivo with positron emission tomography (PET). Methods Brain PET using bolus injection of [18F]FNDP followed by emission imaging lasting 90 or 180 min was completed in healthy adults (5 males, 2 females, ages 40–53 years). The kinetic behavior of [18F]FNDP was evaluated using a radiometabolite-corrected arterial plasma input function with compartmental or graphical modeling approaches. Results [18F]FNDP PET was without adverse effects. Akaike information criterion favored the two-tissue compartment model (2TCM) in all ten regions of interest. Regional total distribution volume (VT) values from each compartmental model and Logan analysis were generally well identified except for corpus callosum VT using the 2TCM. Logan analysis was assessed as the choice model due to stability of regional VT values from 90-min data and due to high correlation of Logan-derived regional VT values with those from the 2TCM. [18F]FNDP binding was higher in human cerebellar cortex and thalamus relative to supratentorial cortical regions, which aligns with reported expression patterns of the epoxide hydrolase 2 gene in human brain. Conclusion These data support further use of [18F]FNDP PET to study sEH in human brain.Keywords
Funding Information
- National Institute on Aging (AG054802)
- National Institute of Biomedical Imaging and Bioengineering (EB024495)
- Johns Hopkins University
This publication has 13 references indexed in Scilit:
- PET imaging of soluble epoxide hydrolase in non-human primate brain with [18F]FNDPEJNMMI Research, 2020
- Humble beginnings with big goals: Small molecule soluble epoxide hydrolase inhibitors for treating CNS disordersProgress in Neurobiology, 2018
- Soluble epoxide hydrolase plays a key role in the pathogenesis of Parkinson’s diseaseProceedings of the National Academy of Sciences of the United States of America, 2018
- An optimized radiosynthesis of [18F]FNDP, a positron emission tomography radiotracer for imaging soluble epoxide hydrolase (sEH)Journal of Labelled Compounds and Radiopharmaceuticals, 2018
- 18F-FNDP for PET Imaging of Soluble Epoxide HydrolaseJournal of Nuclear Medicine, 2016
- Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stressProceedings of the National Academy of Sciences of the United States of America, 2016
- Soluble epoxide hydrolase activity regulates inflammatory responses and seizure generation in two mouse models of temporal lobe epilepsyBrain, Behavior, and Immunity, 2015
- Consensus Nomenclature for in vivo Imaging of Reversibly Binding RadioligandsJournal of Cerebral Blood Flow & Metabolism, 2007
- Statistical dynamic image reconstruction in state-of-the-art high-resolution PETPhysics in Medicine & Biology, 2005
- Graphical Analysis of Reversible Radioligand Binding from Time—Activity Measurements Applied to [N-11C-Methyl]-(−)-Cocaine PET Studies in Human SubjectsJournal of Cerebral Blood Flow & Metabolism, 1990