title: One-pot two-step radiosynthesis of a new (18)F-labeled thiol reactive prosthetic group and its conjugate for insulinoma imaging.
abstract: N-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-6-fluoronicotinamide ([(18)F]FNEM), a novel prosthetic agent that is thiol-specific, was synthesized using a one-pot two-step strategy: (1) (18)F incorporation by a nucleophilic displacement of trimethylammonium substrate under mild conditions; (2) amidation of the resulting 6-[(18)F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester with N-(2-aminoethyl)maleimide trifluoroacetate salt. The radiosynthesis of the maleimide tracer was completed in 75 min from [(18)F]fluoride with 26 ± 5% decay uncorrected radiochemical yield, and specific activity of 19-88 GBq/μmol (decay uncorrected). The in vitro cell uptake, in vivo biodistribution, and positron emission tomography (PET) imaging properties of its conjugation product with [Cys(40)]-exendin-4 were described. [(18)F]FNEM-Cys(40)-exendin-4 showed specific targeting of glucagon-like peptide 1 receptor (GLP-1R) positive insulinomas and comparable imaging results to our recently reported [(18)F]FPenM-Cys(40)-exendin-4.
authors.affiliation: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , 35A Convent Drive, Bethesda, Maryland 20892, United States.
authors.forename: Xuyi
authors.initials: X
authors.lastname: Yue
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yan
authors.forename: Chenxi
authors.initials: C
authors.lastname: Wu
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.forename: Baozhong
authors.initials: B
authors.lastname: Shen
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D004195:Disease Models, Animal; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D000067757:Glucagon-Like Peptide-1 Receptor; D020128:Inhibitory Concentration 50; D007340:Insulinoma / Q000000981:diagnostic imaging*; D051379:Mice; D008807:Mice, Inbred BALB C; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D049268:Positron-Emission Tomography; D018027:Receptors, Glucagon / Q000378:metabolism; D013388:Succinimides / Q000138:chemical synthesis*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013696:Temperature; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; C000599880:N-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-6-fluoronicotinamide; D018027:Receptors, Glucagon; D013388:Succinimides; D013438:Sulfhydryl Compounds; D009536:Niacinamide
keywords: fluorine-18; insulinoma imaging; thiol reactive prosthetic group