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

Abstract 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 18 F–labeled glucaric acid (FGA) for PET imaging of isoproterenol-induced cardiomyopathy in a rat model. Methods We synthesized 18 F–FGA by controlled oxidation of 18 F–fluorodeoxy glucose (FDG), mediated by 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) in presence of NaBr and NaOCl in highly-buffered reaction conditions. After ascertaining preferential uptake of 18 F–FGA in necrotic as compared to normal H9c2 myoblasts, the biodistribution and circulation kinetics of 18 F–FGA was assessed in mice. Moreover, the potential of 18 F–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 18 F–FGA was accomplished by a 5min, one step oxidation of 18 F–FDG. Reaction yield was quantitative and no side-products were detected. Biodistribution studies showed rapid elimination from the body ( k e =0.83h −1 ); the major organ of 18 F–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 18 F–FGA, whereas healthy hearts showed negligible uptake of 18 F–FGA. Target-to-nontarget contrast for 18 F–FGA accumulation became significantly more pronounced in 4h images as compared to images acquired 1h post-injection. Conclusion 18 F–FGA can be easily and quantitatively synthesized from ubiquitously available 18 F–FDG as a precursor. The resultant 18 F–FGA has a potential to serve as an infarct-avid agent for PET imaging of MI. Advances in Knowledge and Implications for Patient Care 18 F–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.