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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chelating Agents / chemical synthesis
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Chelating Agents / chemistry
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Chelating Agents / pharmacokinetics
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Gallium Radioisotopes / chemistry*
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Gallium Radioisotopes / pharmacokinetics
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Heterocyclic Compounds / chemical synthesis
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Heterocyclic Compounds / chemistry*
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Heterocyclic Compounds / pharmacokinetics
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Heterocyclic Compounds, 1-Ring
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Hyaluronic Acid / chemical synthesis
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Hyaluronic Acid / chemistry*
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Hyaluronic Acid / pharmacokinetics
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Kinetics
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Male
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Myocardial Infarction / diagnosis
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Oligonucleotides / chemical synthesis
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Oligonucleotides / chemistry*
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Oligonucleotides / pharmacokinetics
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Positron-Emission Tomography / methods*
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Rats
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Rats, Sprague-Dawley
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Tissue Distribution
Substances
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Chelating Agents
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Gallium Radioisotopes
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Heterocyclic Compounds
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Heterocyclic Compounds, 1-Ring
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Oligonucleotides
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1,4,7-triazacyclononane-N,N',N''-triacetic acid
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Hyaluronic Acid