Hernández-Gil Javier, Braga Marta, Harriss Bethany I, Carroll Laurence S, Leow Chee Hau, Tang Meng-Xing, Aboagye Eric O, Long Nicholas J
Department of Chemistry , Imperial College London , UK . Email:
Department of Surgery & Cancer , Imperial College London , UK . Email:
Chem Sci. 2019 May 1;10(21):5603-5615. doi: 10.1039/c9sc00684b. eCollection 2019 Jun 7.
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 whole-body imaging can hamper the development of new MB formulations. Herein, we describe a fast and efficient method for achieving Ga-labelling of MBs after a direct comparison of two different strategies. The optimised approach produces Ga-labelled MBs in good yields through the bioorthogonal inverse-electron-demand Diel-Alder reaction between a -cyclooctene-modified phospholipid and a new tetrazine-bearing HBED-CC chelator. The ability to noninvasively study the whole-body distribution of Ga-labelled MBs was demonstrated using positron emission tomography (PET). This method could be broadly applicable to other phospholipid-based formulations, providing accessible solutions for tracking of MBs.
微泡（MB）造影剂彻底改变了超声（US）成像在临床和临床前的应用方式。超声造影增强了软组织对比度，还具备在分子水平可视化疾病进程的能力。然而，其无法提供全身成像可能会阻碍新型微泡制剂的研发。在此，我们通过直接比较两种不同策略，描述了一种快速高效的实现微泡镓标记的方法。优化后的方法通过α-环辛烯修饰的磷脂与一种新型含四嗪的HBED-CC螯合剂之间的生物正交逆电子需求狄尔斯-阿尔德反应，以良好的产率生成镓标记的微泡。使用正电子发射断层扫描（PET）证明了无创研究镓标记微泡全身分布的能力。该方法可广泛应用于其他基于磷脂的制剂，为微泡追踪提供可行的解决方案。
