title: Copper-free click chemistry with the short-lived positron emitter fluorine-18.
abstract: The copper-free strain-promoted click chemistry between (18)F-labeled aza-dibenzocyclooctyne [(18)F]FB-DBCO and various azides is described. [(18)F]FB-DBCO was prepared in 85% isolated radiochemical yield (decay-corrected) through acylation of amino aza-dibenzocyclooctyne 1 with N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB). [(18)F]FB-DBCO showed promising radiopharmacological profil with fast blood clearance as assessed with dynamic small animal PET studies. Metabolic stability of [(18)F]FB-DBCO was 60% of intact compound after 60 min post injection in normal Balb/C mice and blood clearance half-life was determined to be 53 s based on the time-activity-curve (TAC). Copper-free click chemistry was performed with various azides at low concentrations (1-2 μM) which differed in their structural complexity in different solvents (methanol, water, phosphate buffer and in bovine serum albumin (BSA) solution). Reaction proceeded best in methanol (>95% yield after 15 min at room temperature), whereas reaction in BSA required longer reaction times of 60 min and 40 °C upon completion.
authors.affiliation: Department of Oncology, University of Alberta, 11560 University Ave, Edmonton, AB T6G 1Z2, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bouvet
authors.forename: Melinda
authors.initials: M
authors.lastname: Wuest
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
mesh_terms: D000480:Alkynes / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001372:Aza Compounds / Q000737:chemistry* / Q000378:metabolism; D001386:Azides / Q000737:chemistry* / Q000378:metabolism; D057930:Click Chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000480:Alkynes; D001372:Aza Compounds; D001386:Azides; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals