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-O-(2-[(18)F]fluoroethyl)-6-O-desmethyl-diprenorphine ([(18)F]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 [(18)F]FE-DPN for positron emission tomography (PET) studies of μ-opioid receptors. Herein, we report an optimized direct nucleophilic (18)F-fluorination and the deprotection conditions for a fully automated radiosynthesis of [(18)F]FE-DPN on a modified GE Tracerlab FX FE synthesis panel. Starting from 1-1.5 GBq of [(18)F]fluoride and applying an Oasis Max 1cc cartridge for fluorine-18 trapping with a reduced amount of K(2)CO(3) (5.06 μmol K(+) ion), [(18)F]FE-DPN ([(18)F]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.