Synthesis, radiolabeling with fluorine-18 and preliminary in vivo evaluation of a heparan sulphate mimetic as potent angiogenesis and heparanase inhibitor for cancer applications

Org Biomol Chem. 2016 Feb 14;14(6):1915-20. doi: 10.1039/c5ob02513c.

Abstract

Heparan Sulfate (HS) mimetics are able to block crucial interactions of the components of the extracellular matrix in angiogenic processes and as such, represent a valuable class of original candidates for cancer therapy. Here we first report the synthesis and in vitro angiogenic inhibition properties of a conjugated, novel and rationally-designed octasaccharide-based HS mimetic. We also herein report its labeling with fluorine-18 and present the preliminary in vivo Positron Emission Tomography imaging data in rats. This constitutes one of the rare examples of labeling and in vivo evaluation of a synthetic, polysaccharide-based, macromolecule.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use*
  • Fluorine Radioisotopes
  • Glucuronidase / antagonists & inhibitors*
  • Glucuronidase / metabolism
  • Heparitin Sulfate / chemistry*
  • Humans
  • Male
  • Molecular Structure
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / diagnosis*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Polysaccharides / chemistry
  • Positron-Emission Tomography
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Fluorine Radioisotopes
  • Polysaccharides
  • Heparitin Sulfate
  • heparanase
  • Glucuronidase