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6-O-(2-[18F]Fluoroethyl)-6-O-Desmethyl-Diprenorphine ([18F]FE-DPN) Preferentially Binds to Mu Opioid Receptors In Vivo

Abstract

Purpose

6-O-(2-[18F]Fluoroethyl)-6-O-desmethyl-diprenorphine ([18F]FE-DPN) is regarded as a non-selective opioid receptor radiotracer.

Procedure

Here, we report the first characterization of [18F]FE-DPN synthesized from the novel precursor, 6-O-(2-tosyloxyethoxy)-6-O-desmethyl-3-O-trityl-diprenorphine (TE-TDDPN), using a one-pot, two-step nucleophilic radiosynthesis to image opioid receptors in rats and mice using positron emission tomography.

Results

We also show that [18F]FE-DPN and [3H]DPN exhibit negligible brain uptake in mu opioid receptor (MOR) knockout mice.

Conclusions

Taken together with prior findings, our results suggest that [18F]FE-DPN and [3H]DPN preferentially bind to MOR in rodents in vivo.

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Funding

This work was supported by the NIDA Intramural Research Program (ZIA000069, MM) and by Grants RYC-2019-027371-I (JB) funded by MCIN/AEI/1013039/501100011033 and by “ESF Investing in your future,” Plan Nacional Sobre Drogas 2021I070 (JB) funded by the Spanish Ministerio de Sanidad, and (EB024495, MGP) funded by NIBIB.

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Authors and Affiliations

Authors

Contributions

Designed and performed experiments, analyzed data, and wrote the manuscript: MRL, MM. Designed experiments, analyzed data, and wrote the manuscript: JB. Designed and performed experiments: ENV, JLG, DH. Performed experiments: RCB. Contributed resources and reagents: MJ, GH, RFD, MGP, CAZ. All coauthors reviewed the manuscript and provided comments.

Corresponding author

Correspondence to Michael Michaelides.

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Conflict of Interest

MM has received research funding from AstraZeneca, Redpin Therapeutics, and Attune Neurosciences. CAZ is listed as a coinventor on a patent for the use of ketamine in major depression and suicidal ideation. CAZ is listed as a coinventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydro and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain. CAZ is listed as coinventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. CAZ has assigned his patent rights to the US government but will share a percentage of any royalties that may be received by the government. All other authors declare no conflicts of interest.

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Levinstein, M.R., Ventriglia, E.N., Gomez, J.L. et al. 6-O-(2-[18F]Fluoroethyl)-6-O-Desmethyl-Diprenorphine ([18F]FE-DPN) Preferentially Binds to Mu Opioid Receptors In Vivo. Mol Imaging Biol (2022). https://doi.org/10.1007/s11307-022-01767-5

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  • DOI: https://doi.org/10.1007/s11307-022-01767-5

Key words

  • Diprenorphine
  • PET
  • Opioid
  • In vivo