A Feasibility Study of [¹⁸F]F-AraG Positron Emission Tomography (PET) for Cardiac Imaging-Myocardial Viability in Ischemia-Reperfusion Injury Model

Purpose: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, ¹⁸F-labeled 2'-deoxy-2'-¹⁸F-fluoro-9-β-d-arabinofuranosylguanine ([¹⁸F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI.

Procedure: To test whether the myocardial [¹⁸F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [¹⁸F]F-AraG uptake in normal heart by comparing [¹⁸F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [¹⁸F]F-AraG and 2-deoxy-2[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [¹⁸F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis.

Results: The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [¹⁸F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [¹⁸F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [¹⁸F]FDG signals showed wider variability at different time points. Noticeable [¹⁸F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates.

Conclusions: Our preliminary preclinical data show that [¹⁸F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.