title: High-resolution imaging with (99m)Tc-glucarate for assessing myocardial injury in rat heart models exposed to different durations of ischemia with reperfusion.
abstract: (99m)Tc-Glucarate ((99m)Tc-GLA) is a novel infarct-avid imaging agent. The aim of this study was to evaluate the role of (99m)Tc-GLA for assessing the severity of myocardial ischemia-reperfusion injury in rat heart models exposed to varied durations of left coronary artery (LCA) occlusion with reperfusion using a high-resolution SPECT system, FASTSPECT. We also wanted to clarify whether a rapid sequence of 3-dimensional imaging with FASTSPECT can quantify uptake and washout kinetics of cardiovascular imaging agents in small-animal heart models.
  
  
  METHODS
  The ischemic-reperfused rat heart models were created by ligating the LCA for 30 min (IR30, n = 12) or 90 min (IR90, n = 6) (IR = ischemia-reperfusion) and releasing the ligature for 30 min. Dynamic images were acquired over a 2-h period after (99m)Tc-GLA was intravenously injected. The ischemic area at risk (IAR) was determined by Evans blue staining. Necrosis was assessed with triphenyltetrazolium chloride (TTC) staining and a transmission electron microscope (TEM).
  
  
  RESULTS
  The infarct size of the left ventricle (% IAR) on TTC staining was smaller in IR30 (49.2 +/- 4.3) than in IR90 (73.4 +/- 4.7, P < 0.05), which exhibited evidence of more severe irreversible injury than the IR30 heart on TEM. FASTSPECT images demonstrated hot spot accumulations of (99m)Tc-GLA in all hearts. The washout of (99m)Tc-GLA from the ischemic-reperfused area in IR90 was significantly slower than that in IR30. The ratio of the hot spot to normal myocardial activity was 4.1 +/- 0.3 in IR30 and 7.1 +/- 1.1 in IR90 (P < 0.05). The hot spot size (% IAR) (58.4 +/- 2.7 in IR30 vs. 75.9 +/- 2.7 in IR90, P < 0.05) related significantly to the infarct size.
  
  
  CONCLUSIONS
  The severity of myocardial injury induced by ischemia-reperfusion can be assessed by FASTSPECT imaging with (99m)Tc-GLA. The results suggest that (99m)Tc-GLA will be clinically useful in detecting and quantifying acute necrotic myocardium. The FASTSPECT imaging with the rat heart models provides a solution-specific approach with high-resolution and fast dynamic acquisition for kinetic studies of new myocardial imaging agents.
authors.affiliation: Department of Radiology, The University of Arizona, Tucson, Arizona 85724, USA. zliu@radiology.arizona.edu
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Liu
authors.forename: Harrison H
authors.initials: HH
authors.lastname: Barrett
authors.forename: Gail D
authors.initials: GD
authors.lastname: Stevenson
authors.forename: George A
authors.initials: GA
authors.lastname: Kastis
authors.forename: Michael
authors.initials: M
authors.lastname: Bettan
authors.forename: Lars R
authors.initials: LR
authors.lastname: Furenlid
authors.forename: Donald W
authors.initials: DW
authors.lastname: Wilson
authors.forename: Koon Yan
authors.initials: KY
authors.lastname: Pak
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005937:Glucaric Acid / Q000031:analogs & derivatives*; D006321:Heart / Q000000981:diagnostic imaging; D007089:Image Enhancement / Q000295:instrumentation / Q000379:methods*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000000981:diagnostic imaging*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000000981:diagnostic imaging*; D009206:Myocardium / Q000473:pathology; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C067171:technetium Tc 99m glucarate; D005937:Glucaric Acid