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

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.

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.

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.

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.