Department of Nuclear Medicine, Huashan Hospital, Fudan University, No.12 Urumchi Middle Road, Jing'an District, Shanghai 200040, China.
Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
J Med Chem. 2022 Jan 13;65(1):497-506. doi: 10.1021/acs.jmedchem.1c01660. Epub 2021 Dec 22.
Mitochondria-targeting positron emission tomography (PET) and fluorescent dual-modal probes are rarely reported. As one of the most promising lipophilic cations, F16 and its derivatives (F16s) have never been used for myocardial imaging. In this work, 14 F16s are synthesized and evaluated for cardiac imaging. In vitro cell fluorescence imaging revealed that the lead probe 5MEF is precisely localized in the mitochondria of cardiomyocytes. In addition, it shows excellent ex vivo fluorescence imaging quality with the heart-to-muscle and heart-to-liver ratios up to ∼2. Furthermore, the radiofluorinated probe F-5MEF is successfully prepared and shows a high initial heart uptake of 8.66 ± 0.34 % ID/g at 5 min post injection. It displays a high heart imaging performance, a long retention time in the heart, and a low background in the most normal tissues as revealed by PET. To our knowledge, this is the first time novel F16 analogues are designed and developed for myocardial dual-modal imaging.
线粒体靶向正电子发射断层扫描（PET）和荧光双模探针很少有报道。作为最有前途的亲脂性阳离子之一，F16 及其衍生物（F16s）从未被用于心肌成像。在这项工作中，合成了 14 个 F16s 并对其进行了心脏成像评估。体外细胞荧光成像显示，先导探针 5MEF 精确定位于心肌细胞的线粒体中。此外，它具有出色的离体荧光成像质量，心脏与肌肉和心脏与肝脏的比值高达约 2。此外，放射性氟标记探针 F-5MEF 成功制备，并在注射后 5 分钟时显示出 8.66±0.34%ID/g 的高初始心脏摄取。正电子发射断层扫描显示，它具有较高的心脏成像性能、较长的心脏保留时间和大多数正常组织中的低背景。据我们所知，这是首次设计和开发新型 F16 类似物用于心肌双模成像。
