Jennifer M Coughlin1,2, Stephanie Slania3, Yong Du2, Laura K Shinehouse2, Mary Katherine Brosnan2, Babak Behnam Azad2, Daniel P Holt2, Hong Fan2, Wojciech G Lesniak2, Il Minn2, Steven P Rowe2, Robert F Dannals2, Andrew G Horti2, Martin G Pomper4,5,6. 1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 2. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 3. Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 4. Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA. mpomper@jhmi.edu. 5. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA. mpomper@jhmi.edu. 6. Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD, USA. mpomper@jhmi.edu.
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.
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.
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