title: Imaging of rat cerebral ischemia-reperfusion injury using(99m)Tc-labeled duramycin.
abstract: OBJECTIVE
  Prompt identification of necrosis and apoptosis in the infarct core and penumbra region is critical in acute stroke for delineating the underlying ischemic/reperfusion molecular pathologic events and defining therapeutic alternatives. The objective of this study was to investigate the capability of (99m)Tc-labeled duramycin in detecting ischemia-reperfusion injury in rat brain after middle cerebral artery (MCA) occlusion.
  
  
  METHODS
  Ischemic cerebral injury was induced in ten rats by vascular insertion of a nylon suture in the left MCA for 3 hr followed by 21-24hr reperfusion. After i.v. injection of (99m)Tc-duramycin (1.0-3.5 mCi), dynamic cerebral images were acquired for 1 hr in six rats using a small-animal SPECT imager. Four other rats were imaged at 2 hr post-injection. Ex vivo images were obtained by autoradiography after sacrifice. Histologic analyses were performed to assess cerebral infarction and apoptosis.
  
  
  RESULTS
  SPECT images showed that (99m)Tc-duramycin uptake in the left cerebral hemisphere was significantly higher than that in the right at 1 and 2 hr post-injection. The level of radioactive uptake in the ischemic brain varied based on ischemic severity. The average ratio of left cerebral hot-spot uptake to right hemisphere radioactivity, as determined by computerized ROI analysis, was 4.92±0.79. Fractional washout at 1 hr was 38.2±4.5% of peak activity for left cerebral hot-spot areas and 80.9±2.0% for remote control areas (P<0.001). Based on triphenyltetrazolium chloride staining and autoradiograph image data, the hotspot uptake may be associated primarily with the ischemic penumbra, in which high apoptotic activity was observed by cleaved caspase-3 immunocytochemical staining.
  
  
  CONCLUSIONS
  (99m)Tc-duramycin SPECT imaging may be useful for detecting and quantifying ongoing apoptotic neuronal cell loss induced by ischemia-reperfusion injury.
authors.affiliation: Department of Medical Imaging, The University of Arizona, Tucson, AZ 85724-5067, USA.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Gail D
authors.initials: GD
authors.lastname: Stevenson
authors.forename: Christy
authors.initials: C
authors.lastname: Barber
authors.forename: Lars R
authors.initials: LR
authors.lastname: Furenlid
authors.forename: Harrison H
authors.initials: HH
authors.lastname: Barrett
authors.forename: James M
authors.initials: JM
authors.lastname: Woolfenden
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001430:Bacteriocins; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D007553:Isotope Labeling; D007700:Kinetics; D008297:Male; D015609:Organotechnetium Compounds; D010455:Peptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000000981:diagnostic imaging* / Q000473:pathology; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D001430:Bacteriocins; D015609:Organotechnetium Compounds; D010455:Peptides; C040522:duramycin