Development of Mitochondria-Targeted Small-Molecule Dyes for Myocardial PET and Fluorescence Bimodal Imaging

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 18F-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.