Development of Ga-labelled ultrasound microbubbles for whole-body PET imaging

• Published in: Chemical science (Cambridge) Vol. 1; no. 21; pp. 563 - 5615
• Main Authors: Hernández-Gil, Javier, Braga, Marta, Harriss, Bethany I, Carroll, Laurence S, Leow, Chee Hau, Tang, Meng-Xing, Aboagye, Eric O, Long, Nicholas J
• Format: Journal Article
• Language: English
• Published: 29.05.2019
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c9sc00684b

Microbubble (MB) contrast agents have revolutionalised the way ultrasound (US) imaging can be used clinically and pre-clinically. Contrast-enhanced US offers improvements in soft-tissue contrast, as well as the ability to visualise disease processes at the molecular level. However, its inability to provide in vivo whole-body imaging can hamper the development of new MB formulations. Herein, we describe a fast and efficient method for achieving 68 Ga-labelling of MBs after a direct comparison of two different strategies. The optimised approach produces 68 Ga-labelled MBs in good yields through the bioorthogonal inverse-electron-demand Diel-Alder reaction between a trans -cyclooctene-modified phospholipid and a new tetrazine-bearing HBED-CC chelator. The ability to noninvasively study the whole-body distribution of 68 Ga-labelled MBs was demonstrated in vivo using positron emission tomography (PET). This method could be broadly applicable to other phospholipid-based formulations, providing accessible solutions for in vivo tracking of MBs. We report a rapid and efficient method for labelling ultrasound microbubble (MB) agents with a generator-produced PET isotope using a facile ligation between a trans -cyclooctene-modified phospholipid and a new 68 Ga-HBED-CC-tetrazine tracer. This method provides accessible solutions for in vivo tracking of MBs.