Optimization of a Nucleophilic Two-Step Radiosynthesis of 6- O-(2-[18F]fluoroethyl)-6- O-desmethyl-diprenorphine ([18F]FE-DPN) for PET Imaging of Brain Opioid Receptors

Enikő Németh; Barbara Gyuricza; Viktória Forgács; Paul Cumming; Gjermund Henriksen; János Marton; Beate Bauer; Pál Mikecz; Anikó Fekete

doi:10.3390/ijms241713152

Optimization of a Nucleophilic Two-Step Radiosynthesis of 6- O-(2-[¹⁸F]fluoroethyl)-6- O-desmethyl-diprenorphine ([¹⁸F]FE-DPN) for PET Imaging of Brain Opioid Receptors

Int J Mol Sci. 2023 Aug 24;24(17):13152. doi: 10.3390/ijms241713152.

Authors

Enikő Németh¹, Barbara Gyuricza¹, Viktória Forgács¹, Paul Cumming^{2

3}, Gjermund Henriksen^{4

5

6}, János Marton⁷, Beate Bauer⁷, Pál Mikecz¹, Anikó Fekete¹

Affiliations

¹ Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, H-4032 Debrecen, Hungary.
² Department of Nuclear Medicine, Bern University Hospital, Freiburgstraße 18, CH-3010 Bern, Switzerland.
³ School of Psychology and Counselling, Queensland University of Technology, Brisbane QLD-4059, Australia.
⁴ Norwegian Medical Cyclotron Centre Ltd., Sognsvannsveien 20, N-0372 Oslo, Norway.
⁵ Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway.
⁶ Institute of Physics, University of Oslo, Sem Sælands Vei 24, N-0371 Oslo, Norway.
⁷ ABX Advanced Biochemical Compounds Biomedizinische Forschungsreagenzien GmbH, Heinrich-Glaeser-Strasse 10-14, D-01454 Radeberg, Germany.

Abstract

We have established a method for nucleophilic one-pot, two-step radiosynthesis of the popular opioid receptor radioligand 6-O-(2-[¹⁸F]fluoroethyl)-6-O-desmethyl-diprenorphine ([¹⁸F]FE-DPN) from the novel precursor 6-O-(2-tosyloxyethyl)-6-O-desmethyl- 3-O-trityl-diprenorphine (TE-TDDPN), which we designate as the Henriksen precursor. We undertook an optimization of the synthesis conditions, aiming to enhance the accessibility of [¹⁸F]FE-DPN for positron emission tomography (PET) studies of μ-opioid receptors. Herein, we report an optimized direct nucleophilic ¹⁸F-fluorination and the deprotection conditions for a fully automated radiosynthesis of [¹⁸F]FE-DPN on a modified GE Tracerlab FX FE synthesis panel. Starting from 1-1.5 GBq of [¹⁸F]fluoride and applying an Oasis Max 1cc cartridge for fluorine-18 trapping with a reduced amount of K₂CO₃ (5.06 μmol K⁺ ion), [¹⁸F]FE-DPN ([¹⁸F]11) was produced with 44.5 ± 10.6 RCY (decay-corrected), high radiochemical purity (>99%), and a molar activity of 32.2 ± 11.8 GBq/μmol in 60-65 min.

Keywords: 6,14-ethenomorphinans; 6-O-(2-[18F]fluoroethyl)-6-O-desmethyl-diprenorphine; nucleophilic radiosynthesis; opioid receptors; orvinols; positron emission tomography.

MeSH terms

Brain* / diagnostic imaging
Diprenorphine
Positron-Emission Tomography
Receptors, Opioid*
Receptors, Opioid, mu

Substances

Diprenorphine
Receptors, Opioid
Receptors, Opioid, mu

Grants and funding

This research received no external funding.