PET Study of S1PR1 Expression in Rodent Model of Myocardial Infarction

Area of Science:

• Cardiovascular Research
• Molecular Imaging
• Biomedical Engineering

Background:

• Myocardial infarction (MI) is a major cause of death globally.
• Sphingosine-1-phosphate receptor 1 (S1PR1) is crucial for cardiac health and preventing adverse remodeling post-MI.
• Monitoring S1PR1 dynamics after MI is vital for assessing cardiac remodeling and guiding treatment.

Purpose of the Study:

• To validate the S1PR1 PET radiotracer [18F]FS1P1 for tracking S1PR1 expression changes in vivo.
• To assess the utility of [18F]FS1P1 PET imaging as a non-invasive diagnostic tool for MI.
• To investigate the dynamic changes of S1PR1 expression following myocardial infarction.

Main Methods:

• Characterization of the [18F]FS1P1 radiotracer in an echo-guided mouse model of MI.
• Utilized [18F]FDG PET for infarct delineation and Masson trichrome staining for fibrosis assessment.
• Performed immunofluorescence and autoradiography to correlate PET signal with S1PR1 expression and tissue distribution.

Main Results:

• [18F]FS1P1 uptake significantly decreased in the infarct region (31.8% at 2 days, 37.6% at 2 weeks post-MI) compared to sham controls.
• A 20.8% decrease in [18F]FS1P1 signal was observed in the remote non-infarct area at 2 weeks post-MI.
• PET signal changes directly corresponded with validated alterations in S1PR1 expression via immunofluorescence.

Conclusions:

• Myocardial infarction leads to the downregulation of S1PR1 expression.
• [18F]FS1P1 PET imaging serves as an effective non-invasive tool for quantifying S1PR1 expression changes post-MI.
• This approach offers potential for improved diagnosis and monitoring of cardiac remodeling after MI.