Imaging of rat cerebral ischemia-reperfusion injury using99mTc-labeled duramycin

Yuqing Zhang, Gail D. Stevenson, Christy Barber, Lars R. Furenlid, Harrison H. Barrett, James M. Woolfenden, Ming Zhao, Zhonglin Liu

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Objectives: 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 99mTc-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 3hr followed by 21-24hr reperfusion. After i.v. injection of 99mTc-duramycin (1.0-3.5mCi), dynamic cerebral images were acquired for 1hr in six rats using a small-animal SPECT imager. Four other rats were imaged at 2hr 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 99mTc-duramycin uptake in the left cerebral hemisphere was significantly higher than that in the right at 1 and 2hr 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 1hr 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: 99mTc-duramycin SPECT imaging may be useful for detecting and quantifying ongoing apoptotic neuronal cell loss induced by ischemia-reperfusion injury.

Original languageEnglish (US)
Pages (from-to)80-88
Number of pages9
JournalNuclear Medicine and Biology
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Cerebral ischemia
  • Duramycin
  • SPECT
  • Stroke
  • Tc

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Fingerprint Dive into the research topics of 'Imaging of rat cerebral ischemia-reperfusion injury using<sup>99m</sup>Tc-labeled duramycin'. Together they form a unique fingerprint.

  • Cite this