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.
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Acknowledgements
The authors would like to thank the Johns Hopkins PET Center, Rehab Abdallah for supervising the administrative aspects of this effort, and Alimamy Kargbo for assisting in the RP-HPLC analyses.
Data and materials availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Code availability
Not applicable.
Funding
This work was supported the National Institutes of Health [AG054802 and EB024495 (AGH and MGP)] and a Johns Hopkins University Catalyst award (YD and JMC).
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AH, JC, YD, and MP jointly developed the concept of the manuscript. LS and MKB, together with JC, SR, and MP, led the data acquisition and analyzed these imaging data together with YD and SS. BBA, DH, HF, WL, IM, RD, and AH jointly completed each radiotracer synthesis, as well as the measurement and critical evaluation of radiotracer dynamic behavior in blood plasma. All authors were involved in the writing and proof reading of the manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies involving animals. The study was approved by the Johns Hopkins Investigational Review Board and Radiation Safety Committees. All subjects provided written informed consent.
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Competing interests
AGH and MGP are co-inventors on a US patent covering [18F]FNDP and as such are entitled to a portion of any licensing fees and royalties generated by this technology. JMC is the spouse of MGP. AGH, SPR, and MGP are consultants for Precision Molecular, Inc., which have licensed [18F]FNDP. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies. All other authors have no relevant financial or non-financial interests to disclose.
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Coughlin, J.M., Slania, S., Du, Y. et al. First-in-human neuroimaging of soluble epoxide hydrolase using [18F]FNDP PET. Eur J Nucl Med Mol Imaging 48, 3122–3128 (2021). https://doi.org/10.1007/s00259-021-05231-4
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DOI: https://doi.org/10.1007/s00259-021-05231-4