title: Molecular MRI of acute necrosis with a novel DNA-binding gadolinium chelate: kinetics of cell death and clearance in infarcted myocardium.
abstract: 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.
  
  
  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.affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shuning
authors.initials: S
authors.lastname: Huang
authors.forename: Howard H
authors.initials: HH
authors.lastname: Chen
authors.forename: Hushan
authors.initials: H
authors.lastname: Yuan
authors.forename: Guangping
authors.initials: G
authors.lastname: Dai
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Schuhle
authors.forename: Choukri
authors.initials: C
authors.lastname: Mekkaoui
authors.forename: Soeun
authors.initials: S
authors.lastname: Ngoy
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
authors.forename: Peter
authors.initials: P
authors.lastname: Caravan
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
authors.forename: David E
authors.initials: DE
authors.lastname: Sosnovik
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D001665:Binding Sites; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D019786:Gadolinium DTPA / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008967:Molecular Biology; D009203:Myocardial Infarction / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology; D009336:Necrosis / Q000473:pathology
chemical_list: D004247:DNA; D019786:Gadolinium DTPA