Imaging Imaging of isoproterenol-induced myocardial injury with 18F labeled fluoroglucaric acid in a rat model

Positron emission tomography (PET) of myocardial infarction (MI) by infarct avid imaging has the potential to reduce the time to diagnosis and improve diagnostic accuracy. The objective of this work was to synthesize F-18-labeled glucaric acid (FGA) for PET imaging of isoproterenol-induced cardiomyopathy in a rat model. Methods: We synthesized F-18-FGA by controlled oxidation of F-18-fluorodeoxy glucose (FDG), mediated by 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) in presence of NaBr and NaOCI in highly-buffered reaction conditions. After ascertaining preferential uptake of F-18-FGA in necrotic as compared to normal H9c2 myoblasts, the biodistribution and circulation kinetics of F-18-FGA was assessed in mice. Moreover, the potential of F-18-FGA to image myocardial damage was investigated in a rat model of isoproterenol-induced cardiomyopathy. Isoproterenol-induced myocardial injury was verified at necropsy by tissue staining and plasma cardiac troponin levels. Results: Synthesis of radiochemically pure F-18-FGA was accomplished by a 5 min, one step oxidation of F-18-FDG. Reaction yield was quantitative and no side-products were detected. Biodistribution studies showed rapid elimination from the body (k(e) = 0.83 h(-1)); the major organ of F-18-FGA accumulation was kidney. In the rat model, isoproterenol-treatment resulted in significant increase in cardiac troponin. PET images showed that the hearts of isoproterenol-treated rats accumulated significant amounts of F-18-FGA, whereas healthy hearts showed negligible uptake of F-18-FGA. Target-to-nontarget contrast for F-18-FGA accumulation became significantly more pronounced in 4 h images as compared to images acquired 1 h post-injection. Conclusion: F-18-FGA can be easily and quantitatively synthesized from ubiquitously available F-18-FDG as a precursor. The resultant F-18-FGA has a potential to serve as an infarct-avid agent for PET imaging of MI. Advances in knowledge and implications for patient care: F-18-FGA/PET will complement existing perfusion imaging protocols in therapeutic decision making, determination of revascularization candidacy and success, differentiation of ischemia from necrosis in MI, discrimination of myocarditis from infarction, and surveillance of heart transplant rejection. (C) 2018 Elsevier Inc. All rights reserved.