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