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

The production of F-18-labelled microbubbles (MBs) via the aluminium-[F-18]fluoride ([F-18]AlF) radiolabelling method and facile inverse-electron-demand Diels-Alder (IEDDA) 'click' chemistry is reported. An [F-18]AlF-NODA-labelled tetrazine was synthesised in excellent radiochemical yield (>95% RCY) and efficiently conjugated to a trans-cyclooctene (TCO) functionalised phospholipid (40-50% RCY), which was incorporated into MBs (40-50% RCY). To demonstrate the potential of producing F-18-labelled MBs for clinical studies, we also describe a kit-based approach which is amenable for use in a hospital radiopharmacy setting.