Heart disease continues to be a leading cause of mortality and morbidity across the globe. Positron emission tomography (PET) has slowly become a remarkable technology of a non-invasive technique for accurately diagnosing cardiac diseases.
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PET tracers currently in use have a very short decay half-life, restricting their clinical use. The 18F-labeled probes possess an adequate half-life and have become potential agents for myocardial imaging.
The research team led by Zhen Cheng and Hao Chen from the Molecular Imaging Center of Shanghai Institute of Materia Medica of the Chinese Academy of Sciences developed lipophilic cation compounds for myocardial PET and fluorescence bimodal imaging. The study was published in the Journal of Medicinal Chemistry.
An ex vivo fluorescence imaging method was used by the researchers to evaluate the performance of 14 F16 derivatives in cardiac imaging of mice. They discovered that 5MEF—a leading compound—specifically targets mitochondria in cardiomyocytes, exhibiting the best imaging properties with a heart-to-background ratio, and it is biocompatible without obvious tissue toxicity.
A two-step procedure was used to label the screened-out 5MEF with radionuclide 18F. 18F-5MEF had a high radiochemical yield, a short synthesis time, and a high in vitro stability. Using 18F-5MEF as a PET tracer, microPET analysis was performed for 120 minutes on healthy BALB/c nude mice.
According to the study results, 18F-5MEF demonstrated a high initial heart uptake at 5 minutes post-injection and an extended retention time in the heart within 120 minutes. This makes 18F-5MEF a promising mitochondria-targeting PET probe for heart diseases.
In addition, F16 analogs were developed for dual-modal imaging of the myocardium. With 5MEF, myocardial viability and perfusion can be detected in real-time during heart surgery, helping to guide the procedure. The development of 5MEF may inspire researchers to conduct further studies on designing myocardia-targeting PET probes based on F16s.
Zheng, L., et al. (2021) Development of Mitochondria-Targeted Small-Molecule Dyes for Myocardial PET and Fluorescence Bimodal Imaging. Journal of Medicinal Chemistry. doi.org/10.1021/acs.jmedchem.1c01660.