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Gallium‐68‐labelled NOTA‐oligonucleotides: an optimized method for their preparation
Author(s) -
Gijs Marlies,
Dammicco Sylvestre,
Warnier Corentin,
Aerts An,
Impens Nathalie R.E.N,
D'Huyvetter Matthias,
Léonard Marc,
Baatout Sarah,
Luxen André
Publication year - 2016
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3363
Subject(s) - bioconjugation , chemistry , oligonucleotide , combinatorial chemistry , bifunctional , chelation , aptamer , chromatography , dna , organic chemistry , biochemistry , microbiology and biotechnology , biology , catalysis
One of the most essential aspects to the success of radiopharmaceuticals is an easy and reliable radiolabelling protocol to obtain pure and stable products. In this study, we optimized the bioconjugation and gallium‐68 ( 68 Ga) radiolabelling conditions for a single‐stranded 40‐mer DNA oligonucleotide, in order to obtain highly pure and stable radiolabelled oligonucleotides. Quantitative bioconjugation was obtained for a disulfide‐functionalized oligonucleotide conjugated to the macrocylic bifunctional chelator MMA‐NOTA (maleimido‐mono‐amide (1,4,7‐triazanonane‐1,4,7‐triyl)triacetic acid). Next, this NOTA‐oligonucleotide bioconjugate was radiolabelled at room temperature with purified and pre‐concentrated 68 Ga with quantitative levels of radioactive incorporation and high radiochemical and chemical purity. In addition, high chelate stability was observed in physiological‐like conditions (37 °C, PBS and serum), in the presence of a transchelator (EDTA) and transferrin. A specific activity of 51.1 MBq/nmol was reached using a 1470‐fold molar excess bioconjugate over 68 Ga. This study presents a fast, straightforward and reliable protocol for the preparation of 68 Ga‐radiolabelled DNA oligonucleotides under mild reaction conditions and without the use of organic solvents. The methodology herein developed will be applied to the preparation of oligonucleotidic sequences (aptamers) targeting the human epidermal growth factor receptor 2 (HER2) for cancer imaging.