title: Application of palladium-mediated (18)F-fluorination to PET radiotracer development: overcoming hurdles to translation.
abstract: New chemistry methods for the synthesis of radiolabeled small molecules have the potential to impact clinical positron emission tomography (PET) imaging, if they can be successfully translated. However, progression of modern reactions from the stage of synthetic chemistry development to the preparation of radiotracer doses ready for use in human PET imaging is challenging and rare. Here we describe the process of and the successful translation of a modern palladium-mediated fluorination reaction to non-human primate (NHP) baboon PET imaging-an important milestone on the path to human PET imaging. The method, which transforms [(18)F]fluoride into an electrophilic fluorination reagent, provides access to aryl-(18)F bonds that would be challenging to synthesize via conventional radiochemistry methods.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Kamlet
authors.forename: Constanze N
authors.initials: CN
authors.lastname: Neumann
authors.forename: Eunsung
authors.initials: E
authors.lastname: Lee
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Carlin
authors.forename: Christian K
authors.initials: CK
authors.lastname: Moseley
authors.forename: Nickeisha
authors.initials: N
authors.lastname: Stephenson
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.forename: Tobias
authors.initials: T
authors.lastname: Ritter
mesh_terms: D000818:Animals; D005459:Fluorides / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D054879:Halogenation; D009942:Organometallic Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D010215:Papio; D017374:Paroxetine / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000737:chemistry
chemical_list: D005462:Fluorine Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D058826:Serotonin 5-HT2 Receptor Agonists; D017374:Paroxetine; D010165:Palladium; D005459:Fluorides
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