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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Sep 9

PMID 37685958

Authors

Eniko Nemeth

Barbara Gyuricza

Viktoria Forgacs

Paul Cumming

Gjermund Henriksen

Janos Marton

Beate Bauer

Pal Mikecz

Aniko Fekete

Affiliations

Soon will be listed here.

Abstract

We have established a method for nucleophilic one-pot, two-step radiosynthesis of the popular opioid receptor radioligand 6--(2-[F]fluoroethyl)-6--desmethyl-diprenorphine ([F]FE-DPN) from the novel precursor 6--(2-tosyloxyethyl)-6--desmethyl- 3--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 [F]FE-DPN for positron emission tomography (PET) studies of μ-opioid receptors. Herein, we report an optimized direct nucleophilic F-fluorination and the deprotection conditions for a fully automated radiosynthesis of [F]FE-DPN on a modified GE Tracerlab FX FE synthesis panel. Starting from 1-1.5 GBq of [F]fluoride and applying an Oasis Max 1cc cartridge for fluorine-18 trapping with a reduced amount of KCO (5.06 μmol K ion), [F]FE-DPN ([F]) 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.

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