A1 Refereed original research article in a scientific journal
Synthesis and In Vivo PET Imaging of Hyaluronan Conjugates of Oligonucleotides
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
Publisher: AMER CHEMICAL SOC
Publication year: 2016
Journal: Bioconjugate Chemistry
Volume: 27
Issue: 2
First page : 391
Last page: 403
Number of pages: 13
ISSN: 1043-1802
eISSN: 1520-4812
DOI: https://doi.org/10.1021/acs.bioconjchem.5b00477
Synthesis for 68Ga-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.
