In vivo dynamic imaging of myocardial cell death using 99mTc-labeled C2A domain of synaptotagmin I in a rat model of ischemia and reperfusion

Zhonglin Liu, Ming Zhao, Xiaoguang Zhu, Lars R Furenlid, Yi Chun Chen, Harrison H Barrett

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Abstract

Objectives: This study was designed to investigate the capability of a small-animal SPECT imager, FastSPECT II, for dynamic rat heart imaging and to characterize the in vivo kinetic properties of 99mTc-C2A-glutathione-s-transferase (GST), a molecular probe targeting apoptosis and necrosis, in detecting cell death in ischemic-reperfused rat hearts. Methods: C2A-GST was radiolabeled with 99mTc via 2-iminothiolane thiolation. Myocardial ischemia-reperfusion was induced by 30-min ligation of the left coronary artery followed by 120-min reperfusion in seven rats. FastSPECT II cardiac images of 99mTc-C2A-GST in list-mode acquisition were recorded for 2 h using FastSPECT II. Results: Tomographic images showed a focal radioactive accumulation (hot spot) in the lateral and anterior walls of the left ventricle. The hot spot was initially visualized 10 min after injection and persisted on the 2-h images. Quantitative analysis demonstrated that the hot-spot radioactivity increased significantly within 30 min postinjection and experienced no washout up to the end of the 2-h study. The ratio of the hot spot/viable myocardium was 4.52±0.24, and infarct-to-lung ratio was 8.22±0.63 at 2 h postinjection. The uptake of 99mTc-C2A-GST in the infarcted myocardium was confirmed by triphenyl tetrazolium chloride staining and autoradiography analysis. Conclusions: FastSPECT II allows quantitative dynamic imaging and functional determination of radiotracer kinetics in rat hearts. An in vivo kinetic profile of 99mTc-C2A-GST in the ischemic-reperfused rat heart model was characterized successfully. The pattern of accelerated 99mTc-C2A-GST uptake in the ischemic area at risk after reperfusion may be useful in detecting and quantifying ongoing myocardial cell loss induced by ischemia-reperfusion.

Original languageEnglish (US)
Pages (from-to)907-915
Number of pages9
JournalNuclear Medicine and Biology
Volume34
Issue number8
DOIs
StatePublished - Nov 2007

Fingerprint

Synaptotagmin I
Glutathione Transferase
Reperfusion
Cell Death
Ischemia
Myocardium
Molecular Probes
Myocardial Reperfusion
Single-Photon Emission-Computed Tomography
Autoradiography
Radioactivity
Heart Ventricles
Myocardial Ischemia
Ligation
Chlorides
Coronary Vessels
Necrosis
Apoptosis
Staining and Labeling
Lung

Keywords

  • Apoptosis
  • C2A
  • Heart
  • Necrosis
  • Rat
  • SPECT

ASJC Scopus subject areas

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

Cite this

@article{e31700c7d9604b9a83c088f1e8568fc0,
title = "In vivo dynamic imaging of myocardial cell death using 99mTc-labeled C2A domain of synaptotagmin I in a rat model of ischemia and reperfusion",
abstract = "Objectives: This study was designed to investigate the capability of a small-animal SPECT imager, FastSPECT II, for dynamic rat heart imaging and to characterize the in vivo kinetic properties of 99mTc-C2A-glutathione-s-transferase (GST), a molecular probe targeting apoptosis and necrosis, in detecting cell death in ischemic-reperfused rat hearts. Methods: C2A-GST was radiolabeled with 99mTc via 2-iminothiolane thiolation. Myocardial ischemia-reperfusion was induced by 30-min ligation of the left coronary artery followed by 120-min reperfusion in seven rats. FastSPECT II cardiac images of 99mTc-C2A-GST in list-mode acquisition were recorded for 2 h using FastSPECT II. Results: Tomographic images showed a focal radioactive accumulation (hot spot) in the lateral and anterior walls of the left ventricle. The hot spot was initially visualized 10 min after injection and persisted on the 2-h images. Quantitative analysis demonstrated that the hot-spot radioactivity increased significantly within 30 min postinjection and experienced no washout up to the end of the 2-h study. The ratio of the hot spot/viable myocardium was 4.52±0.24, and infarct-to-lung ratio was 8.22±0.63 at 2 h postinjection. The uptake of 99mTc-C2A-GST in the infarcted myocardium was confirmed by triphenyl tetrazolium chloride staining and autoradiography analysis. Conclusions: FastSPECT II allows quantitative dynamic imaging and functional determination of radiotracer kinetics in rat hearts. An in vivo kinetic profile of 99mTc-C2A-GST in the ischemic-reperfused rat heart model was characterized successfully. The pattern of accelerated 99mTc-C2A-GST uptake in the ischemic area at risk after reperfusion may be useful in detecting and quantifying ongoing myocardial cell loss induced by ischemia-reperfusion.",
keywords = "Apoptosis, C2A, Heart, Necrosis, Rat, SPECT",
author = "Zhonglin Liu and Ming Zhao and Xiaoguang Zhu and Furenlid, {Lars R} and Chen, {Yi Chun} and Barrett, {Harrison H}",
year = "2007",
month = "11",
doi = "10.1016/j.nucmedbio.2007.07.013",
language = "English (US)",
volume = "34",
pages = "907--915",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "8",

}

TY - JOUR

T1 - In vivo dynamic imaging of myocardial cell death using 99mTc-labeled C2A domain of synaptotagmin I in a rat model of ischemia and reperfusion

AU - Liu, Zhonglin

AU - Zhao, Ming

AU - Zhu, Xiaoguang

AU - Furenlid, Lars R

AU - Chen, Yi Chun

AU - Barrett, Harrison H

PY - 2007/11

Y1 - 2007/11

N2 - Objectives: This study was designed to investigate the capability of a small-animal SPECT imager, FastSPECT II, for dynamic rat heart imaging and to characterize the in vivo kinetic properties of 99mTc-C2A-glutathione-s-transferase (GST), a molecular probe targeting apoptosis and necrosis, in detecting cell death in ischemic-reperfused rat hearts. Methods: C2A-GST was radiolabeled with 99mTc via 2-iminothiolane thiolation. Myocardial ischemia-reperfusion was induced by 30-min ligation of the left coronary artery followed by 120-min reperfusion in seven rats. FastSPECT II cardiac images of 99mTc-C2A-GST in list-mode acquisition were recorded for 2 h using FastSPECT II. Results: Tomographic images showed a focal radioactive accumulation (hot spot) in the lateral and anterior walls of the left ventricle. The hot spot was initially visualized 10 min after injection and persisted on the 2-h images. Quantitative analysis demonstrated that the hot-spot radioactivity increased significantly within 30 min postinjection and experienced no washout up to the end of the 2-h study. The ratio of the hot spot/viable myocardium was 4.52±0.24, and infarct-to-lung ratio was 8.22±0.63 at 2 h postinjection. The uptake of 99mTc-C2A-GST in the infarcted myocardium was confirmed by triphenyl tetrazolium chloride staining and autoradiography analysis. Conclusions: FastSPECT II allows quantitative dynamic imaging and functional determination of radiotracer kinetics in rat hearts. An in vivo kinetic profile of 99mTc-C2A-GST in the ischemic-reperfused rat heart model was characterized successfully. The pattern of accelerated 99mTc-C2A-GST uptake in the ischemic area at risk after reperfusion may be useful in detecting and quantifying ongoing myocardial cell loss induced by ischemia-reperfusion.

AB - Objectives: This study was designed to investigate the capability of a small-animal SPECT imager, FastSPECT II, for dynamic rat heart imaging and to characterize the in vivo kinetic properties of 99mTc-C2A-glutathione-s-transferase (GST), a molecular probe targeting apoptosis and necrosis, in detecting cell death in ischemic-reperfused rat hearts. Methods: C2A-GST was radiolabeled with 99mTc via 2-iminothiolane thiolation. Myocardial ischemia-reperfusion was induced by 30-min ligation of the left coronary artery followed by 120-min reperfusion in seven rats. FastSPECT II cardiac images of 99mTc-C2A-GST in list-mode acquisition were recorded for 2 h using FastSPECT II. Results: Tomographic images showed a focal radioactive accumulation (hot spot) in the lateral and anterior walls of the left ventricle. The hot spot was initially visualized 10 min after injection and persisted on the 2-h images. Quantitative analysis demonstrated that the hot-spot radioactivity increased significantly within 30 min postinjection and experienced no washout up to the end of the 2-h study. The ratio of the hot spot/viable myocardium was 4.52±0.24, and infarct-to-lung ratio was 8.22±0.63 at 2 h postinjection. The uptake of 99mTc-C2A-GST in the infarcted myocardium was confirmed by triphenyl tetrazolium chloride staining and autoradiography analysis. Conclusions: FastSPECT II allows quantitative dynamic imaging and functional determination of radiotracer kinetics in rat hearts. An in vivo kinetic profile of 99mTc-C2A-GST in the ischemic-reperfused rat heart model was characterized successfully. The pattern of accelerated 99mTc-C2A-GST uptake in the ischemic area at risk after reperfusion may be useful in detecting and quantifying ongoing myocardial cell loss induced by ischemia-reperfusion.

KW - Apoptosis

KW - C2A

KW - Heart

KW - Necrosis

KW - Rat

KW - SPECT

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