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: Satish Jadhav, Meeri Käkelä, Jussi Mäkilä, Max Kiugel, Heidi Liljenbäck, Jenni Virta, Päivi Poijärvi-Virta, Tiina Laitala-Leinonen, Ville Kytö, Sirpa Jalkanen, Antti Saraste, Anne Roivainen, Harri Lönnberg, Pasi Virta
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 27 Issue 2 Pg. 391-403 (Feb 17 2016) ISSN: 1520-4812 [Electronic] United States
• PMID: 26517303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• Gallium Radioisotopes
• Heterocyclic Compounds
• Heterocyclic Compounds, 1-Ring
• Oligonucleotides
• 1,4,7-triazacyclononane-N,N',N''-triacetic acid
• Hyaluronic Acid

Topics

• Animals
• Chelating Agents (chemical synthesis, chemistry, pharmacokinetics)
• Gallium Radioisotopes (chemistry, pharmacokinetics)
• Heterocyclic Compounds (chemical synthesis, chemistry, pharmacokinetics)
• Heterocyclic Compounds, 1-Ring
• Hyaluronic Acid (chemical synthesis, chemistry, pharmacokinetics)
• Kinetics
• Male
• Myocardial Infarction (diagnosis)
• Oligonucleotides (chemical synthesis, chemistry, pharmacokinetics)
• Positron-Emission Tomography (methods)
• Rats
• Rats, Sprague-Dawley
• Tissue Distribution