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

Marjorie R Levinstein; Emilya N Ventriglia; Juan L Gomez; Reece C Budinich; János Marton; Gjermund Henriksen; Daniel P Holt; Robert F Dannals; Martin G Pomper; Carlos A Zarate Jr; Jordi Bonaventura; Michael Michaelides

doi:10.1007/s11307-022-01767-5

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

Mol Imaging Biol. 2023 Apr;25(2):384-390. doi: 10.1007/s11307-022-01767-5. Epub 2022 Aug 23.

Authors

Affiliations

¹ Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute On Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
² ABX Advanced Biochemical Compounds Biomedizinische Forschungsreagenzien GmbH, Heinrich-Glaeser-Strasse 10-14, 01454, Radeberg, Germany.
³ Institute of Basic Medical Sciences, University of Oslo, Blindern, P. O. Box 1105, N-0317, Oslo, Norway.
⁴ Norwegian Medical Cyclotron Centre Ltd, Sognsvannsveien 20, N-0372, Oslo, Norway.
⁵ Institute of Physics, University of Oslo, Sem Sælands vei 24, N-0371, Oslo, Norway.
⁶ Department of Radiology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
⁷ Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, 20892, USA.
⁸ Departament de Patologia I Terapèutica Experimental, Institut de Neurociències, Universitat de Barcelona, L'Hospitalet de Llobregat, Catalonia, Spain.
⁹ Neuropharmacology and Pain Group, Neuroscience Program, Institut d'Investigació Biomèdica de Bellvitge, IDIBELL, 08907, L'Hospitalet de Llobregat, Catalonia, Spain.
¹⁰ Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute On Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA. mike.michaelides@nih.gov.
¹¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. mike.michaelides@nih.gov.

PMID: 35999424
DOI: 10.1007/s11307-022-01767-5

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.

Keywords: Diprenorphine; In vivo; Opioid; PET.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Animals
Brain / metabolism
Diprenorphine / metabolism
Mice
Positron-Emission Tomography* / methods
Rats
Receptors, Opioid / metabolism
Receptors, Opioid, mu* / metabolism

Substances

Diprenorphine
Receptors, Opioid, mu
Receptors, Opioid

Abstract

Publication types

MeSH terms

Substances

Grants and funding