High-resolution imaging with 99mTc-glucarate for assessing myocardial injury in rat heart models exposed to different durations of ischemia with reperfusion

Zhonglin Liu, Harrison H. Barrett, Gail D. Stevenson, George A. Kastis, Michael Bettan, Lars R. Furenlid, Donald W. Wilson, Yan Pak Koon

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

99mTc-Glucarate (99mTc-GLA) is a novel infarct-avid imaging agent. The aim of this study was to evaluate the role of 99mTc-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 smallanimal 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 99mTc-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 99mTc-GLA in all hearts. The washout of 99mTc-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. Conclusion: The severity of myocardial injury induced by ischemia-reperfusion can be assessed by FASTSPECT imaging with 99mTc-GLA. The results suggest that 99mTc-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.

Original languageEnglish (US)
Pages (from-to)1251-1259
Number of pages9
JournalJournal of Nuclear Medicine
Volume45
Issue number7
StatePublished - Jul 1 2004

Keywords

  • High-resolution SPECT
  • Ischemia-reperfusion injury
  • Rat heart
  • Tc-glucarate

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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