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

doi:10.1016/j.nucmedbio.2007.07.013

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

^*Corresponding author for this work

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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 language	English (US)
Pages (from-to)	907-915
Number of pages	9
Journal	Nuclear Medicine and Biology
Volume	34
Issue number	8
DOIs	https://doi.org/10.1016/j.nucmedbio.2007.07.013
State	Published - Nov 2007

Funding

The authors wish to acknowledge the technical support of Christy Barber and the editorial assistance of Corrie Thies. This work was supported by NIH Grant P41 EB002035 and an American Heart Association grant.

Keywords

Apoptosis
C2A
Heart
Necrosis
Rat
SPECT

ASJC Scopus subject areas

Molecular Medicine
Radiology Nuclear Medicine and imaging
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.nucmedbio.2007.07.013

Cite this

@article{77091185a9cd49349b577affb3de86f4,

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.}",

note = "Funding Information: The authors wish to acknowledge the technical support of Christy Barber and the editorial assistance of Corrie Thies. This work was supported by NIH Grant P41 EB002035 and an American Heart Association grant.",

year = "2007",

month = nov,

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 B.V.",

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.

N1 - Funding Information: The authors wish to acknowledge the technical support of Christy Barber and the editorial assistance of Corrie Thies. This work was supported by NIH Grant P41 EB002035 and an American Heart Association grant.

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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