title: Synthesis and In Vivo PET Imaging of Hyaluronan Conjugates of Oligonucleotides.
abstract: Synthesis for (68)Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-chelated oligonucleotide hyaluronan (HA) tetra- and hexasaccharide conjugates is described. A solid-supported technique is used to introduce NOTA-chelator into the 3'-terminus of oligonucleotides and a copper-free strain promoted azide alkyne cycloaddition (SPAAC) to HA/oligonucleotide conjugation. Protecting group manipulation, required for the HA-moieties, is carried out after the SPAAC-conjugation. Positron emission tomography (PET) is used (1) in the whole-body distribution kinetic studies of the conjugates in healthy rats and (2) to show the potential of hyaluronan-induced targeting of oligonucleotides into the infarcted area of rats with myocardial infarction.
authors.affiliation: Department of Chemistry, University of Turku , FI-20014 Turku, Finland.
authors.forename: Satish
authors.initials: S
authors.lastname: Jadhav
authors.forename: Meeri
authors.initials: M
authors.lastname: Käkelä
authors.forename: Jussi
authors.initials: J
authors.lastname: Mäkilä
authors.forename: Max
authors.initials: M
authors.lastname: Kiugel
authors.forename: Heidi
authors.initials: H
authors.lastname: Liljenbäck
authors.forename: Jenni
authors.initials: J
authors.lastname: Virta
authors.affiliation: Department of Chemistry, University of Turku , FI-20014 Turku, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Poijärvi-Virta
authors.forename: Tiina
authors.initials: T
authors.lastname: Laitala-Leinonen
authors.forename: Ville
authors.initials: V
authors.lastname: Kytö
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.affiliation: Department of Chemistry, University of Turku , FI-20014 Turku, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Lönnberg
authors.affiliation: Department of Chemistry, University of Turku , FI-20014 Turku, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Virta
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D005710:Gallium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D009203:Myocardial Infarction / Q000175:diagnosis; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D009841:Oligonucleotides; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D006820:Hyaluronic Acid