Researchers Constructed Novel PET and Fluorescence Bimodal Small-Molecule Probes for Myocardial Imaging

Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Positron emission tomography (PET) has gradually become a significant technology of noninvasive measurement in accurate diagnosis and prognosis of cardiac disease. The currently PET tracers have an extremely short decay half-life, which limits the use in clinic. 18F-labeled probes have an appropriate physical half-life, and have became potential myocardial imaging agents.

In a study published in Journal of Medicinal Chemistry on Dec. 22, researchers led by CHENG Zhen and CHEN Hao from Molecular Imaging Center of Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, developed mitochondria-targeting lipophilic cation compounds for myocardial PET and fluorescence bimodal imaging.

The researchers synthesized 14 F16 derivatives, and evaluated their performance in cardiac imaging using ex vivo fluorescence imaging method in mice. The leading compound 5MEF specifically targeted mitochondria in cardiomyocytes and exhibited best imaging properties with a heart-to-background ratio, and was biocompatible without apparent tissue toxicity.

Then, the screened-out 5MEF was labeled with radionuclide 18F through two-step procedure. 18F-5MEF had a high radiochemical yield, less synthesis time and high in vitro stability. MicroPET analysis using 18F-5MEF as PET tracer was performed in healthy BALB/c nude mice for 120 minutes. The results illustrated that 18F-5MEF showed excellent myocardial accumulation properties for PET imaging with a high initial heart uptake at 5 min post injection and a long retention time in heart within 120 min. In result, 18F-5MEF is a promising mitochondria-targeting PET probe for cardiac diseases.

The F16 analogues were innovatively designed and developed for myocardial dual-modal imaging. 5MEF can provide real-time detection of myocardial viability and myocardial perfusion to guide the operation in heart surgery. The successful development of 5MEF may inspire more research on the design of myocardia-targeting PET probes based on F16s.

DOI: https://doi.org/10.1021/acs.jmedchem.1c01660

Contact:
DIAO Wentong

Shanghai Institute of Materia Medica, Chinese Academy of Sciences

E-mail: diaowentong@simm.ac.cn