title: Synthesis and evaluation of an 18F-labelled norbornene derivative for copper-free click chemistry reactions.
abstract: The copper-free click chemistry reaction between norbornene and tetrazine species is known to proceed in a rapid, reliable and selective manner under mild conditions. Due to these attractive properties, this reaction has recently been explored as a generally applicable method of bioconjugation. Here, we report a convenient synthetic procedure towards a novel (18)F-labelled norbornene derivative ([(18)F]NFB) and have evaluated its ability to undergo strain-promoted copper-free click chemistry reactions with two model tetrazine species: an asymmetric dipyridyl tetrazine derivative (Tz) and a tetrazine thiourea-coupled stabilised bombesin peptide (TT-BBN). In both cases, [(18)F]NFB was found to undergo rapid and high-yielding click chemistry reactions. Furthermore, as reactions of this type could also potentially be used in vivo to facilitate the development of a novel pretargeting approach for tumour imaging and therapy, we have also assessed the radiopharmacological profile (bioavailability, biodistribution, blood clearance and metabolic stability) of [(18)F]NFB in normal BALB/c mice. This radiolabelled compound exhibits both high bioavailability and metabolic stability with approximately 90% remaining intact up to 30 min following administration.
authors: Department of Oncology, University of Alberta, 11560 University Ave, Edmonton, AB T6G 1Z2, Canada.
authors: James C
authors: JC
authors: Knight
authors: Susan
authors: S
authors: Richter
authors: Melinda
authors: M
authors: Wuest
authors: Jenilee D
authors: JD
authors: Way
authors: Frank
authors: F
authors: Wuest
mesh_terms: D000818:Animals; D001839:Bombesin / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D057930:Click Chemistry; D003300:Copper; D004355:Drug Stability; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009636:Norbornanes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000737:chemistry; D049268:Positron-Emission Tomography
chemical_list: D005462:Fluorine Radioisotopes; D009636:Norbornanes; D010446:Peptide Fragments; C046060:2-norbornene; D003300:Copper; D001839:Bombesin