Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, W12 0BZ, UK.
School of Biomedical Engineering and Imaging Sciences, King's College London, 4th Floor Lambeth Wing, St Thomas' Hospital, London, SE1 7EH, UK.
Dalton Trans. 2020 Jan 28;49(4):1097-1106. doi: 10.1039/c9dt02354b. Epub 2019 Dec 24.
Radiolabelled lipophilic cations could potentially be used to non-invasively image mitochondrial dysfunction in cardiovascular disease, building on their current role as perfusion imaging agents. We have synthesised and radiolabelled two series of DO2A-based radiotracers, with bistriarylphosphonium- and bisaryl-functionalisation respectively, with gallium-68 to form lipophilic cations. Both sets of tracers radiolabel with over 90% RCP, although the tracers form kinetic/thermodynamic pairs of species upon gallium chelation that can be visualised and separated by radioHPLC. Log D values above -0.3 are observed for the most lipophilic examples of each series of radiotracers. Both tracers show significant preferential uptake in healthy cardiac tissue over cardiac tissue depolarised by CCCP.
基于其作为灌注成像剂的现有作用，放射性标记的亲脂性阳离子有可能被用于非侵入性地成像心血管疾病中的线粒体功能障碍。我们已经合成并放射性标记了两个基于 DO2A 的放射性示踪剂系列，分别具有双芳基膦盐和双芳基官能化，并用镓-68 形成亲脂性阳离子。这两组示踪剂的放射性标记率均超过 90%RCP，尽管示踪剂在镓螯合时形成动力学/热力学的物种对，可以通过放射性 HPLC 进行可视化和分离。观察到每个放射性示踪剂系列中最亲脂性的例子的 LogD 值均高于-0.3。两种示踪剂均显示出在 CCCP 去极化的健康心脏组织中比心脏组织有明显的优先摄取。
