Synthesis and In Vivo PET Imaging of Hyaluronan Conjugates of Oligonucleotides

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• 作者：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
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：February 17, 2016
• 年：2016
• 卷：27
• 期：2
• 页码：391-403
• 全文大小：811K
• ISSN：1520-4812

文摘

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.