Novel Method for Radiolabeling and Dimerizing Thiolated Peptides Using (18)F-Hexafluorobenzene

Bioconjug Chem. 2015 Oct 21;26(10):2016-20. doi: 10.1021/acs.bioconjchem.5b00278. Epub 2015 Jun 24.

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.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Fluorine Radioisotopes / chemistry*
  • Fluorocarbons / chemistry*
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Isotope Labeling / methods*
  • Mice, Nude
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Oligopeptides / pharmacokinetics
  • Peptides / chemistry*
  • Peptides / metabolism
  • Peptides / pharmacokinetics*
  • Positron-Emission Tomography / methods
  • Protein Multimerization
  • Radiopharmaceuticals
  • Sulfhydryl Compounds / chemistry
  • Temperature
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Fluorine Radioisotopes
  • Fluorocarbons
  • Integrin alphaVbeta3
  • Oligopeptides
  • Peptides
  • Radiopharmaceuticals
  • Sulfhydryl Compounds
  • arginyl-glycyl-aspartic acid
  • hexafluorobenzene