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- Title
Noninvasive Molecular Imaging of Cell Death in Myocardial Infarction using <sup>111</sup>In-GSAO.
- Authors
Nobuhiro Tahara; Zandbergen, H. Reinier; de Haas, Hans J.; Petrov, Artiom; Pandurangi, Raghu; Takayoshi Yamaki; Jun Zhou; Tsutomu Imaizumi; Slart, Riemer H. J. A.; Dyszlewski, Mary; Tiziano Scarabelli; Kini, Annapoorna; Reutelingsperger, Chris; Narula, Navneet; Fuster, Valentin; Narula, Jagat
- 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 cardio-myocyte 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 intra-cellularly, 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. 111In-GSAO uptake was observed within the regions of apoptosis seeking agent- 99mTc-Annexin A5 uptake, suggesting the colocalization of apoptotic and necrotic cell death processes.
- Subjects
CELL death -- Risk factors; MYOCARDIAL infarction; HEART cells; DITHIOLS; RADIONUCLIDE imaging
- Publication
Scientific Reports, 2014, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep06826