title: Facile synthesis of para-[(18)F]fluorohippurate via iodonium ylide-mediated radiofluorination for PET renography.
abstract: para-[(18)F]fluorohippurate ([(18)F]PFH) is a renal tubular agent suitable for conducting positron emission tomography (PET) renography. [(18)F]PFH is currently synthesized by a four-step two-pot procedure utilizing a classical prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate, followed by glycine conjugation. Considering the short half-life of fluorine-18 (110min), it is important to reduce the number of synthetic steps and overall production time for successful translation of any fluorine-18 radiopharmaceutical in to clinical practice. Here, we report a new two-step one-pot procedure using a novel spirocyclic iodonium ylide precursor for producing a dose of [(18)F]PFH suitable for human use in 45min including HPLC purification with an overall decay-corrected radiochemical yield of 46.4±2.9% (n=3) and radiochemical purity of >99%.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Room 301, Oklahoma City, OK 73117, USA.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Nkepang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Room 301, Oklahoma City, OK 73117, USA.
authors.forename: Andria F
authors.initials: AF
authors.lastname: Hedrick
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Room 301, Oklahoma City, OK 73117, USA.
authors.forename: Vibhudutta
authors.initials: V
authors.lastname: Awasthi
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Room 301, Oklahoma City, OK 73117, USA. Electronic address: hgali@ouhsc.edu.
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Gali
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes; D054879:Halogenation; D006626:Hippurates / Q000138:chemical synthesis*; D009861:Onium Compounds / Q000138:chemical synthesis*; D049268:Positron-Emission Tomography; D011866:Radioisotope Renography; D017207:Rats, Sprague-Dawley
chemical_list: C541416:4-fluorohippuric acid; D005462:Fluorine Radioisotopes; D006626:Hippurates; D009861:Onium Compounds
keywords: Iodonium; PET; Renography; Ylide; [(18)F]PFH