Gallium-68-labelled NOTA-oligonucleotides: an optimized method for their preparation

Area of Science:

• Nuclear medicine
• Radiopharmaceutical chemistry
• Molecular biology

Background:

• Radiopharmaceuticals require efficient radiolabeling for purity and stability.
• Developing reliable protocols for radiolabeled DNA oligonucleotides is crucial for molecular imaging.

Purpose of the Study:

• To optimize bioconjugation and Gallium-68 (Ga-68) radiolabeling of a DNA oligonucleotide.
• To achieve high purity, stability, and specific activity for Ga-68 labeled oligonucleotides.

Main Methods:

• Conjugation of a disulfide-functionalized oligonucleotide to MMA-NOTA (maleimido-mono-amide (1,4,7-triazanonane-1,4,7-triyl)triacetic acid).
• Room temperature radiolabeling with purified and pre-concentrated Ga-68.
• Assessment of chelate stability under physiological conditions and in the presence of transchelators.

Main Results:

• Quantitative bioconjugation and radiolabeling were achieved.
• High radiochemical and chemical purity of the Ga-68 labeled oligonucleotide was obtained.
• Excellent chelate stability was demonstrated in vitro.
• A specific activity of 51.1 MBq/nmol was reached.

Conclusions:

• A fast, straightforward, and reliable protocol for Ga-68 radiolabeled DNA oligonucleotides was developed under mild conditions.
• The protocol avoids organic solvents, simplifying preparation.
• This methodology is suitable for developing targeted radiopharmaceuticals, such as aptamers for HER2-positive cancer imaging.