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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 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 2013

Funding

The authors are grateful to Edward Abril from Tissue Acquisition and Cellular/Molecular Analysis Shared Service (TACMASS), which is supported by the Arizona Cancer Center Support Grant ( NIH CA023074 ), for generating the immunohistochemical and histological data. We would like to thank Dr. Raymond Nagle at TACMASS for review and discussion of our histological data. We are thankful to Li Wan for assistance in animal studies. This work was supported by NIH grants 5P41-EB002035 and 5R01-HL102085 .

Keywords

  • Cerebral ischemia
  • Duramycin
  • SPECT
  • Stroke
  • Tc

ASJC Scopus subject areas

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

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