Design and synthesis of an ¹⁸F-labeled version of phenylethyl orvinol ([¹⁸F]FE-PEO) for PET-imaging of opioid receptors.

The semisynthetic oripavine derivative phenethyl orvinol (PEO), a full agonist at opioid receptors (OR), is an attractive structural motif for developing ¹⁸F-labeled PET tracers with a high degree of sensitivity for competition between endogenous and exogenous OR-ligands. The target cold reference compound 6-O-(2-fluoroethyl)-6-O-desmethylphenylethyl orvinol (FE-PEO) was obtained via two separate reaction routes. A three-step synthesis was developed for the preparation of a tosyloxyethyl precursor (TE-TDPEO), the key precursor for a direct, nucleophilic radiofluorination to yield [¹⁸F]FE-PEO. The developed radiosynthesis provides the target compound in relevantly high yield and purity, and is adaptable to routine production.