A kit-based aluminium-[¹⁸F]fluoride approach to radiolabelled microbubbles

Area of Science:

• Radiochemistry
• Bioconjugation Chemistry
• Materials Science

Background:

• Developing novel radiolabeling methods is crucial for advancing molecular imaging techniques.
• Microbubbles (MBs) are valuable contrast agents for various imaging modalities.
• Efficient and reliable methods for incorporating radioisotopes into MBs are needed for clinical translation.

Purpose of the Study:

• To report the production of 18F-labelled microbubbles using a combination of [18F]AlF radiolabelling and inverse-electron-demand Diels-Alder (IEDDA) click chemistry.
• To demonstrate a facile and efficient method for synthesizing 18F-labelled MBs suitable for potential clinical use.
• To present a kit-based approach for producing 18F-MBs in a hospital radiopharmacy setting.

Main Methods:

• Synthesis of an [18F]AlF-NODA-labelled tetrazine.
• Conjugation of the tetrazine to a trans-cyclooctene (TCO) functionalized phospholipid via IEDDA click chemistry.
• Incorporation of the functionalized phospholipid into microbubbles.

Main Results:

• The [18F]AlF-NODA-labelled tetrazine was synthesized with an excellent radiochemical yield (>95% RCY).
• Efficient conjugation of the tetrazine to the TCO-functionalized phospholipid was achieved (40-50% RCY).
• The final 18F-labelled microbubbles were produced with a radiochemical yield of 40-50%.

Conclusions:

• The study successfully demonstrates the production of 18F-labelled microbubbles using [18F]AlF radiolabelling and IEDDA click chemistry.
• The developed method is efficient and provides high radiochemical yields, making it suitable for potential clinical applications.
• A kit-based approach was established, highlighting the feasibility of producing these 18F-MBs in a clinical radiopharmacy setting.