title: Novel Method for Radiolabeling and Dimerizing Thiolated Peptides Using (18)F-Hexafluorobenzene.
abstract: Hexafluorobenzene (HFB) reacts with free thiols to produce a unique and selective perfluoroaromatic linkage between two sulfurs. We modified this chemical reaction to produce dimeric (18)F-RGD-tetrafluorobenzene (TFB)-RGD, an integrin αvβ3 receptor ligand. (18)F-HFB was prepared by a fluorine exchange reaction using K(18)F/K2.2.2 at room temperature. The automated radiofluorination was optimized to minimize the amount of HFB precursor and, thus, maximize the specific activity. (18)F-HFB was isolated by distillation and subsequently reacted with thiolated c(RGDfk) peptide under basic and reducing conditions. The resulting (18)F-RGD-TFB-RGD demonstrated integrin receptor specific binding, cellular uptake, and in vivo tumor accumulation.(18)F-HFB can be efficiently incorporated into thiol-containing peptides at room temperature to provide novel imaging agents.
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda, Maryland 20892 United States.
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda, Maryland 20892 United States.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yan
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda, Maryland 20892 United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda, Maryland 20892 United States.
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda, Maryland 20892 United States.
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda, Maryland 20892 United States.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods*; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D055503:Protein Multimerization; D019275:Radiopharmaceuticals; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013696:Temperature; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D005462:Fluorine Radioisotopes; D005466:Fluorocarbons; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010455:Peptides; D019275:Radiopharmaceuticals; D013438:Sulfhydryl Compounds; C047981:arginyl-glycyl-aspartic acid; C003005:hexafluorobenzene