PET Study of S1PR1 Expression in Rodent Model of Myocardial Infarction.

PURPOSE: Acute myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator influencing numerous physiological processes. S1PR1 is the predominant isoform of the S1P receptor in cardiomyocytes and vascular endothelial cells. S1PR1 plays a critical role in preventing adverse cardiac remodeling. The importance of S1PR1 in cardiac physiology has led to the development of novel treatments for MI, including S1PR1 gene delivery strategies aimed at preventing heart failure. Monitoring the dynamic changes of S1PR1 post-MI is clinically significant for assessing cardiac remodeling. This study validated the ability of specific S1PR1 PET radiotracer [18F]FS1P1 to track changes in this signaling pathway, thereby providing a non-invasive diagnostic tool to quantify S1PR1 expression for investigating MI in vivo.

PROCEDURES: We characterized the S1PR1 radiotracer [18F]FS1P1 in an echo-guided mouse model of MI. [18F]FDG PET was used to delineate the infarct area. Masson trichrome staining was used to identify cardiac fibrosis. Immunofluorescence (IF) experiment was conducted to demonstrate changes in S1PR1 expression after MI. Autoradiography was performed to evaluate the distribution of [18F]FS1P1 in MI heart tissues. MI (n = 4) and sham (n = 4) mice were scanned with [18F]FS1P1 PET at 2 days and 2 weeks post-MI, radioactivity uptake in the myocardium was calculated as the percentage of the injected dose per gram (%ID/g).

RESULTS

The uptake of [18F]FS1P1 was significantly decreased by 31.8% in the infarct region at 2 days post-MI compared to the sham group (1.3 ± 0.3 vs. 1.9 ± 0.3), and decreased by 37.6% at 2 weeks post-MI (1.2 ± 0.5). Additionally, [18F]FS1P1 signal decreased by 20.8% in the non-infarct remote area at 2 weeks post-MI compared with the sham control (1.6 ± 0.4 vs. 2.0 ± 0.2). Autoradiography study confirmed the trend of decreased [18F]FS1P1 uptake in the MI tissues. IF studies confirmed that the change in the [18F]FS1P1 PET signal corresponded with the change in S1PR1 expression.

CONCLUSIONS

This study demonstrated the downregulation of S1PR1 expression following MI and validated the use of [18F]FS1P1 PET imaging as an effective tool for detecting changes in S1PR1 expression post-MI.