Development of a bifunctional chelating agent containing isothiocyanate residue for one step F-18 labeling of peptides and application for RGD labeling

Bioorg Med Chem. 2012 Oct 1;20(19):5941-7. doi: 10.1016/j.bmc.2012.07.050. Epub 2012 Aug 7.

Abstract

We report herein a novel isothiocyanate active ligand for fluorine-18 labeling prepared by four step synthesis. It can be conjugated to a target molecule containing an amino functional group under weak basic conditions by way of thiourea bond formation. We explored the application of synthesized ligand by conjugating to well known α(v)β(3) integrin targeting peptide, c(RGDyK). The conjugated peptide showed good radiochemical yield and efficiency with an excellent radiochemical purity (97.1 ± 1.2%) in a short reaction time (10 min). Labeled peptide showed excellent in vitro and in vivo stability (>95%). α(v)β(3) integrin specific tumor uptake was observed both in biodistribution and small animal microPET studies on α(v)β(3)-positive U87MG (human glioma cells) xenograft bearing mice. In general, successful application of synthesized ligand for labeling of RGD peptide could facilitate the possibility of using this ligand for labeling peptides containing an amino functional group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chelating Agents* / chemical synthesis
  • Chelating Agents* / chemistry
  • Fluorine Radioisotopes* / chemistry
  • Glioma / diagnostic imaging*
  • Humans
  • Integrin alphaVbeta3 / analysis*
  • Isothiocyanates* / chemical synthesis
  • Isothiocyanates* / chemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oligopeptides* / chemical synthesis
  • Oligopeptides* / chemistry
  • Positron-Emission Tomography

Substances

  • Chelating Agents
  • Fluorine Radioisotopes
  • Integrin alphaVbeta3
  • Isothiocyanates
  • Oligopeptides
  • isothiocyanic acid
  • arginyl-glycyl-aspartic acid