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, F-labeled 2'-deoxy-2'-F-fluoro-9-β-d-arabinofuranosylguanine ([F]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 [F]-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 knockout ( KO) mice. We assessed the effect of dietary nucleotides on myocardial [F]F-AraG uptake in normal heart by comparing [F]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 [F]F-AraG and 2-deoxy-2[F]fluoro-D-glucose ([F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [F]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 KO and WT mice was not significant ( = ns) indicating that the [F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides ( = ns). The [F]FDG signals showed wider variability at different time points. Noticeable [F]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 [F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.