title: Synthesis, radiolabeling with fluorine-18 and preliminary in vivo evaluation of a heparan sulphate mimetic as potent angiogenesis and heparanase inhibitor for cancer applications.
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.
authors.affiliation: CEA, Institut d'imagerie biomédicale, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91400 Orsay, France. bertrand.kuhnast@cea.fr and Laboratoire IMIV UMR 1023 Inserm/CEA/Université Paris Sud, ERL 9218 CNRS, Université Paris Saclay, 4 place du Général Leclerc, 91400 Orsay, France.
authors.forename: B
authors.initials: B
authors.lastname: Kuhnast
authors.affiliation: Endotis Pharma, Biocitech Park, 102 avenue Gaston Roussel, 93230 Romainville, France and CarboMimetics, 2 rue François Mouthon, 91380 Chilly-Mazarin, France.
authors.forename: A
authors.initials: A
authors.lastname: El Hadri
authors.affiliation: CEA, Institut d'imagerie biomédicale, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91400 Orsay, France. bertrand.kuhnast@cea.fr and Laboratoire IMIV UMR 1023 Inserm/CEA/Université Paris Sud, ERL 9218 CNRS, Université Paris Saclay, 4 place du Général Leclerc, 91400 Orsay, France.
authors.forename: R
authors.initials: R
authors.lastname: Boisgard
authors.affiliation: CEA, Institut d'imagerie biomédicale, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91400 Orsay, France. bertrand.kuhnast@cea.fr.
authors.forename: F
authors.initials: F
authors.lastname: Hinnen
authors.affiliation: Endotis Pharma, Biocitech Park, 102 avenue Gaston Roussel, 93230 Romainville, France.
authors.forename: S
authors.initials: S
authors.lastname: Richard
authors.affiliation: Endotis Pharma, Biocitech Park, 102 avenue Gaston Roussel, 93230 Romainville, France.
authors.forename: A
authors.initials: A
authors.lastname: Caravano
authors.affiliation: Endotis Pharma, Biocitech Park, 102 avenue Gaston Roussel, 93230 Romainville, France.
authors.forename: V
authors.initials: V
authors.lastname: Nancy-Portebois
authors.affiliation: Endotis Pharma, Biocitech Park, 102 avenue Gaston Roussel, 93230 Romainville, France.
authors.forename: M
authors.initials: M
authors.lastname: Petitou
authors.affiliation: Laboratoire PARCC UMR 970 Inserm/Université Paris Descartes, Sorbonne Paris Cité, Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 56 rue Leblanc, 75015 Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Tavitian
authors.affiliation: CEA, Institut d'imagerie biomédicale, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91400 Orsay, France. bertrand.kuhnast@cea.fr and Laboratoire IMIV UMR 1023 Inserm/CEA/Université Paris Sud, ERL 9218 CNRS, Université Paris Saclay, 4 place du Général Leclerc, 91400 Orsay, France.
authors.forename: F
authors.initials: F
authors.lastname: Dollé
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D005462:Fluorine Radioisotopes; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D011134:Polysaccharides / Q000737:chemistry; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D000099175:Heparanase
chemical_list: D004791:Enzyme Inhibitors; D005462:Fluorine Radioisotopes; D005966:Glucuronidase; D006497:Heparan Sulfate; D011134:Polysaccharides; D000099175:Heparanase