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Molecular MRI of acute necrosis with a novel dna-binding gadolinium chelate: kinetics of cell death and clearance in infarcted myocardium

Authors
Journal
Journal of Cardiovascular Magnetic Resonance
1097-6647
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Volume
13
Identifiers
DOI: 10.1186/1532-429x-13-s1-o23
Keywords
  • Oral Presentation
Disciplines
  • Medicine
  • Pharmacology

Abstract

Molecular MRI of acute necrosis with a novel dna-binding gadolinium chelate: kinetics of cell death and clearance in infarcted myocardium ORAL PRESENTATION Open Access Molecular MRI of acute necrosis with a novel dna-binding gadolinium chelate: kinetics of cell death and clearance in infarcted myocardium Shuning Huang1*, Howard H Chen1, Hushan Yuan2, Guangping Dai1, Daniel Schule1, Soeun Ngoy3, Ronglih Liao3, Peter Caravan1, Lee Josephson1, David Sosnovik1 From 2011 SCMR/Euro CMR Joint Scientific Sessions Nice, France. 3-6 February 2011 Objective In the current study, we describe a novel approach to image acute necrotic cell death in vivo through the use of a DNA-binding gadolinium chelate (Gd-TO). Background Detecting cell death in vivo is extremely important in understanding disease pathogenesis, assessing disease progression, and evaluating treatment efficacy. Various MRI techniques have been developed over the years to image cell death. However, most of these techniques are based largely on non-specific pharmacokinetics and accumulation, and usually cannot discriminate acute and chronic injury. Here we present a novel DNA-bind- ing gadolinium chelate (Gd-TO) that binds specifically to the exposed DNA of ruptured/necrotic cells. We show that Gd-TO can be used to selectively detect and image the kinetics of acute necrotic cell death and the subsequent clearance of necrotic debris from injured tissue. Material and methods In vivo imaging was performed in twenty infarcted (permanent ligation of the left coronary artery) C57BL6 mice. The infarcted mice were injected with 0.1 mmol/kg of Gd-TO (15 mice) or Gd-DTPA (5 mice) at varying times post-infarction. MRI was per- formed 2-3 hours after probe injection on a 9.4T scan- ner (Biospin, Bruker) with a gradient strength of 150 Gauss/cm. A modified cardiac gated Look-Locker FISP sequence (TR: 3000ms, TE 1.3, MTX: 160x160, FOV: 2.5 x 2.5 cm2) was used to detect changes in signal intensity and the longitudinal relaxation rate (R1)

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