ABSTRACT
We report the synthesis and biological evaluation of a triplet of 6-O-(18)F-fluoroethylated derivatives of structurally related orvinols that span across the full range of intrinsic activities, the antagonist diprenorphine, the partial agonist buprenorphine, and the full agonist phenethyl-orvinol. [(18)F]fluoroethyl-diprenorphine, [(18)F]fluoroethyl-buprenorphine, and [(18)F]fluoroethyl-phenethyl-orvinol were prepared in high yields and quality from their 6-O-desmethyl-precursors. The results indicate suitable properties of the three 6-O-(18)F-fluoroethylated derivatives as functional analogues to the native carbon-11 labeled versions with similar pharmacological properties.
Subject(s)
Buprenorphine/analogs & derivatives , Diprenorphine/analogs & derivatives , Morphinans/chemical synthesis , Radiopharmaceuticals/chemical synthesis , Animals , Brain/diagnostic imaging , Brain/metabolism , Buprenorphine/chemical synthesis , Buprenorphine/chemistry , Buprenorphine/pharmacokinetics , CHO Cells , Carbon Radioisotopes , Cricetulus , Diprenorphine/chemical synthesis , Diprenorphine/chemistry , Diprenorphine/pharmacokinetics , Fluorine Radioisotopes , Humans , Morphinans/chemistry , Morphinans/pharmacokinetics , Narcotic Antagonists , Positron-Emission Tomography , Radioligand Assay , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacokinetics , Rats , Receptors, Opioid/agonists , Receptors, Opioid/metabolism , Structure-Activity RelationshipABSTRACT
We have developed a new method for automated production of 2-[18F]fluoroethyl tosylate ([18F]FETos) that enables 18F-alkylation to provide PET tracers with high chemical purity. The method is based on the removal of excess ethylene glycol bistosylate precursor by precipitation and subsequent filtration and purification of the filtrate by means of solid phase extraction cartridges (SPE). The method is integrated to a single synthesis module and thereby provides the advantage over previous methods of not requiring HPLC purification, as demonstrated by the full radiosynthesis of the potent opioid receptor PET tracer [18F]fluoroethyldiprenorphine.