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

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.