INTRODUCTION: Myocardial infarction is the leading cause of death in western countries, and positron emission tomography (PET) plays an increasing role in the diagnosis and treatment planning for this disease. However, the absence of an (18)F-labeled PET myocardial perfusion tracer hampers the widespread use of PET in myocardial perfusion imaging (MPI). We recently reported a potential MPI agent based on (18)F-labeled rhodamine B. The goal of this study was to more completely define the biological properties of (18)F-labeled rhodamine B with respect to uptake and localization in an animal model of myocardial infarction and to evaluate the uptake (18)F-labeled rhodamine B by cardiomyocytes. METHODS: A total of 12 female Sprague Dawley rats with a permanent ligation of the left anterior descending artery (LAD) were studied with small-animal PET. The animals were injected with 100-150 μCi of (18)F-labeled rhodamine B diethylene glycol ester ([(18)F]RhoBDEGF) and imaged two days before ligation. The animals were imaged again two to ten days post-ligation. After the post-surgery scans, the animals were euthanized and the hearts were sectioned into 1mm slices and myocardial infarct size was determined by phosphorimaging and 2,3,5-triphenyltetrazolium chloride staining (TTC). In addition, the uptake of [(18)F]RhoBDEGF in isolated rat neonatal cardiomyocytes was determined by fluorescence microscopy. RESULTS: Small-animal PET showed intense and uniform uptake of [(18)F]RhoBDEGF throughout the myocardium in healthy rats. After LAD ligation, well defined perfusion defects were observed in the PET images. The defect size was highly correlated with the infarct size as determined ex vivo by phosphorimaging and TTC staining. In vitro, [(18)F]RhoBDEGF was rapidly internalized into rat cardiomyocytes with ~40 % of the initial activity internalized within the 60 min incubation time. Fluorescence microscopy clearly demonstrated localization of [(18)F]RhoBDEGF in the mitochondria of rat cardiomyocytes. CONCLUSION: Fluorine-18-labeled rhodamine B diethylene glycol ester ([(18)F]RhoBDEGF) provides excellent image quality and clear delineation of myocardial infarcts in a rat infarct model. In vitro studies demonstrate localization of the tracer in the mitochondria of cardiac myocytes. In combination, these results support the continued evaluation of this tracer for the PET assessment of myocardial perfusion.
INTRODUCTION:Myocardial infarction is the leading cause of death in western countries, and positron emission tomography (PET) plays an increasing role in the diagnosis and treatment planning for this disease. However, the absence of an (18)F-labeled PET myocardial perfusion tracer hampers the widespread use of PET in myocardial perfusion imaging (MPI). We recently reported a potential MPI agent based on (18)F-labeled rhodamine B. The goal of this study was to more completely define the biological properties of (18)F-labeled rhodamine B with respect to uptake and localization in an animal model of myocardial infarction and to evaluate the uptake (18)F-labeled rhodamine B by cardiomyocytes. METHODS: A total of 12 female Sprague Dawley rats with a permanent ligation of the left anterior descending artery (LAD) were studied with small-animal PET. The animals were injected with 100-150 μCi of (18)F-labeled rhodamine B diethylene glycol ester ([(18)F]RhoBDEGF) and imaged two days before ligation. The animals were imaged again two to ten days post-ligation. After the post-surgery scans, the animals were euthanized and the hearts were sectioned into 1mm slices and myocardial infarct size was determined by phosphorimaging and 2,3,5-triphenyltetrazolium chloride staining (TTC). In addition, the uptake of [(18)F]RhoBDEGF in isolated rat neonatal cardiomyocytes was determined by fluorescence microscopy. RESULTS: Small-animal PET showed intense and uniform uptake of [(18)F]RhoBDEGF throughout the myocardium in healthy rats. After LAD ligation, well defined perfusion defects were observed in the PET images. The defect size was highly correlated with the infarct size as determined ex vivo by phosphorimaging and TTC staining. In vitro, [(18)F]RhoBDEGF was rapidly internalized into rat cardiomyocytes with ~40 % of the initial activity internalized within the 60 min incubation time. Fluorescence microscopy clearly demonstrated localization of [(18)F]RhoBDEGF in the mitochondria of rat cardiomyocytes. CONCLUSION:Fluorine-18-labeled rhodamine B diethylene glycol ester ([(18)F]RhoBDEGF) provides excellent image quality and clear delineation of myocardial infarcts in a ratinfarct model. In vitro studies demonstrate localization of the tracer in the mitochondria of cardiac myocytes. In combination, these results support the continued evaluation of this tracer for the PET assessment of myocardial perfusion.
Authors: Silvia H D Lacerda; Bindu Abraham; Thomas C Stringfellow; Guilherme L Indig Journal: Photochem Photobiol Date: 2005 Nov-Dec Impact factor: 3.421
Authors: Lars Husmann; Mischa Wiegand; Ines Valenta; Oliver Gaemperli; Tiziano Schepis; Patrick T Siegrist; Mehdi Namdar; Christophe A Wyss; Hatem Alkadhi; Philipp A Kaufmann Journal: Int J Cardiovasc Imaging Date: 2007-12-25 Impact factor: 2.357
Authors: Mark D Bartholomä; Vijay Gottumukkala; Shaohui Zhang; Amanda Baker; Patricia Dunning; Frederic H Fahey; S Ted Treves; Alan B Packard Journal: J Med Chem Date: 2012-12-14 Impact factor: 7.446
Authors: D P Piwnica-Worms; J F Kronauge; A LeFurgey; M Backus; D Hockett; P Ingram; M Lieberman; B L Holman; A G Jones; A Davison Journal: Magn Reson Imaging Date: 1994 Impact factor: 2.546
Authors: Daniel S Berman; Jamshid Maddahi; B K Tamarappoo; Johannes Czernin; Raymond Taillefer; James E Udelson; C Michael Gibson; Marybeth Devine; Joel Lazewatsky; Gajanan Bhat; Dana Washburn Journal: J Am Coll Cardiol Date: 2012-12-19 Impact factor: 24.094
Authors: Hossam M Sherif; Antti Saraste; Eliane Weidl; Axel W Weber; Takahiro Higuchi; Sybille Reder; Thorsten Poethko; Gjermund Henriksen; David Casebier; Simon Robinson; Hans-Jürgen Wester; Stephan G Nekolla; Markus Schwaiger Journal: Circ Cardiovasc Imaging Date: 2009-01-26 Impact factor: 7.792
Authors: Douglas B Cowan; Rouan Yao; Vamsidhar Akurathi; Erin R Snay; Jerusha K Thedsanamoorthy; David Zurakowski; Maria Ericsson; Ingeborg Friehs; Yaotang Wu; Sidney Levitsky; Pedro J Del Nido; Alan B Packard; James D McCully Journal: PLoS One Date: 2016-08-08 Impact factor: 3.240