Document Detail


Molecular MRI of acute necrosis with a novel DNA-binding gadolinium chelate: kinetics of cell death and clearance in infarcted myocardium.
MedLine Citation:
PMID:  21836081     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Current techniques to image cell death in the myocardium are largely nonspecific. We report the use of a novel DNA-binding gadolinium chelate (Gd-TO) to specifically detect the exposed DNA in acutely necrotic (ruptured) cells in vivo.
METHODS AND RESULTS: In vivo MRI was performed in 20 mice with myocardial infarction (MI). The mice were injected with Gd-TO or Gd-DTPA at varying time points after MI. MRI was performed 2 hours after probe injection, to avoid nonspecific signal from the late gadolinium enhancement effect. Cell rupture (Gd-TO uptake) was present within 2 hours of infarction but peaked 9 to 18 hours after the onset of injury. A significant increase in the longitudinal relaxation rate (R(1)) in the infarct was seen in mice injected with Gd-TO within 48 hours of MI, but not in those injected more than 72 hours after MI (R(1)=1.24±0.08 and 0.92±0.03 s(-1), respectively, P<0.001). Gd-DTPA, unlike Gd-TO, washed completely out of acute infarcts within 2 hours of injection (P<0.001). The binding of Gd-TO to exposed DNA in acute infarcts was confirmed with fluorescence microscopy.
CONCLUSIONS: Gd-TO specifically binds to acutely necrotic cells and can be used to image the mechanism and chronicity of cell death in injured myocardium. Cell rupture in acute MI begins early but peaks many hours after the onset of injury. The ruptured cells are efficiently cleared by the immune system and are no longer present in the myocardium 72 hours after injury.
Authors:
Shuning Huang; Howard H Chen; Hushan Yuan; Guangping Dai; Daniel T Schuhle; Choukri Mekkaoui; Soeun Ngoy; Ronglih Liao; Peter Caravan; Lee Josephson; David E Sosnovik
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-08-11
Journal Detail:
Title:  Circulation. Cardiovascular imaging     Volume:  4     ISSN:  1942-0080     ISO Abbreviation:  Circ Cardiovasc Imaging     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-17     Completed Date:  2012-01-23     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  101479935     Medline TA:  Circ Cardiovasc Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  729-37     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Analysis of Variance
Animals
Binding Sites
Cell Death / drug effects
DNA / metabolism
Disease Models, Animal
Gadolinium DTPA / diagnostic use*,  metabolism
Magnetic Resonance Imaging / methods*
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Molecular Biology
Myocardial Infarction / pathology*
Myocytes, Cardiac / pathology*,  physiology
Necrosis / pathology
Grant Support
ID/Acronym/Agency:
P41RR14075/RR/NCRR NIH HHS; R01 EB011996/EB/NIBIB NIH HHS; R01 EB011996/EB/NIBIB NIH HHS; R01 HL093038/HL/NHLBI NIH HHS; R01 HL093038/HL/NHLBI NIH HHS; R01 HL093038-04/HL/NHLBI NIH HHS; S10RR025563/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
9007-49-2/DNA; K2I13DR72L/Gadolinium DTPA
Comments/Corrections

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