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

20 Citations (Scopus)

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

Fingerprint

Reperfusion Injury
Brain Ischemia
Single-Photon Emission-Computed Tomography
Injections
Reperfusion
Apoptosis
Staining and Labeling
Middle Cerebral Artery Infarction
Nylons
Cerebral Infarction
Middle Cerebral Artery
Brain
Cerebrum
Autoradiography
Caspase 3
Radioactivity
Sutures
Blood Vessels
Necrosis
Stroke

Keywords

  • Tc
  • Cerebral ischemia
  • Duramycin
  • SPECT
  • Stroke

ASJC Scopus subject areas

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

Cite this

Imaging of rat cerebral ischemia-reperfusion injury using99mTc-labeled duramycin. / Zhang, Yuqing; Stevenson, Gail D.; Barber, Christy; Furenlid, Lars R; Barrett, Harrison H; Woolfenden, James M.; Zhao, Ming; Liu, Zhonglin.

In: Nuclear Medicine and Biology, Vol. 40, No. 1, 01.2013, p. 80-88.

Research output: Contribution to journalArticle

Zhang, Yuqing ; Stevenson, Gail D. ; Barber, Christy ; Furenlid, Lars R ; Barrett, Harrison H ; Woolfenden, James M. ; Zhao, Ming ; Liu, Zhonglin. / Imaging of rat cerebral ischemia-reperfusion injury using99mTc-labeled duramycin. In: Nuclear Medicine and Biology. 2013 ; Vol. 40, No. 1. pp. 80-88.
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AU - Stevenson, Gail D.

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AU - Furenlid, Lars R

AU - Barrett, Harrison H

AU - Woolfenden, James M.

AU - Zhao, Ming

AU - Liu, Zhonglin

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