title: Noninvasive molecular imaging of cell death in myocardial infarction using 111In-GSAO.
abstract: Acute insult to the myocardium is associated with substantial loss of cardiomyocytes during the process of myocardial infarction. In this setting, apoptosis (programmed cell death) and necrosis may operate on a continuum. Because the latter is characterized by the loss of sarcolemmal integrity, we propose that an appropriately labeled tracer directed at a ubiquitously present intracellular moiety would allow non-invasive definition of cardiomyocyte necrosis. A trivalent arsenic peptide, GSAO (4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid), is capable of binding to intracellular dithiol molecules such as HSP90 and filamin-A. Since GSAO is membrane impermeable and dithiol molecules abundantly present intracellularly, we propose that myocardial localization would represent sarcolemmal disruption or necrotic cell death. In rabbit and mouse models of myocardial infarction and post-infarct heart failure, we employed In-111-labelled GSAO for noninvasive radionuclide molecular imaging. (111)In-GSAO uptake was observed within the regions of apoptosis seeking agent- (99m)Tc-Annexin A5 uptake, suggesting the colocalization of apoptotic and necrotic cell death processes.
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tahara
authors.affiliation: Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
authors.forename: H Reinier
authors.initials: HR
authors.lastname: Zandbergen
authors.affiliation: 1] Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York [2] Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: de Haas
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Artiom
authors.initials: A
authors.lastname: Petrov
authors.affiliation: Covidien Imaging Solutions, Hazelwood, Missouri.
authors.forename: Raghu
authors.initials: R
authors.lastname: Pandurangi
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Yamaki
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Riemer H J A
authors.initials: RH
authors.lastname: Slart
authors.affiliation: Covidien Imaging Solutions, Hazelwood, Missouri.
authors.forename: Mary
authors.initials: M
authors.lastname: Dyszlewski
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Scarabelli
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Annapoorna
authors.initials: A
authors.lastname: Kini
authors.affiliation: Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: Reutelingsperger
authors.affiliation: Department of Pathology, Weill Cornell Medical College, New York, NY.
authors.forename: Navneet
authors.initials: N
authors.lastname: Narula
authors.affiliation: 1] Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York [2] Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
mesh_terms: D000818:Animals; D017304:Annexin A5; D001152:Arsenicals; D004195:Disease Models, Animal; D005978:Glutathione / Q000031:analogs & derivatives*; D007204:Indium; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging / Q000379:methods*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011817:Rabbits; D011877:Radionuclide Imaging; D013667:Technetium
chemical_list: C426645:4-(N-(S-glutathionylacetyl)amino)phenylarsenoxide; D017304:Annexin A5; D001152:Arsenicals; D007204:Indium; D013667:Technetium; D005978:Glutathione