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99mTc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

99mTc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine 99mTc-glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury.

Methods

Twenty-two perfused rat hearts were studied: controls (n = 5), stunned (n = 5; 20-min no-flow followed by 5-min reflow), hibernating (n = 6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n = 6; 120-min no-flow followed by reflow). 99mTc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability.

Results

99mTc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50 ± 0.09) (cpm, SEM) than in control (1.74 ± 0.07), stunned (1.68 ± 0.11), and hibernating (1.59 ± 0.11) (p < 0.05). Tracer retention curves for ischemic-reperfused were elevated at all time points as compared with the other groups. 99mTc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60 ± 0.63) than in control (1.98 ± 0.15), stunned (1.79 ± 0.08), and hibernating (2.33 ± 0.15) (p < 0.05). The 60-min well-counted tracer activity ratio of ischemic-reperfused to control was 9:1 and corroborated the NaI detector results. Creatine kinase, triphenyltetrazolium chloride, and electron microscopy all demonstrated significantly greater injury in ischemic-reperfused compared to the other groups. An excellent correlation was observed between viability markers and tracer activity (r = 0.99 triphenyltetrazolium chloride; r = 0.90 creatine kinase).

Conclusion

99mTc-glucarate activity continually and progressively increased in irreversibly injured myocardium. 99mTc-glucarate uptake was strongly correlated with myocardial necrosis as determined by three independent assessments of viability. There were minimal and similar 99mTc-glucarate uptakes in control, stunned, and hibernating myocardium.

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Acknowledgements

This study was supported in part by grants from the American Heart Association, the William K. Warren Medical Research Institute, and the Anne and Henry Zarrow Foundation. This study is dedicated to the William K. Warren family and the Anne and Henry Zarrow family for their support of medical research, without which these experiments would not have been possible. We are indebted to William Meek Ph.D. for his help in the presentation of the EM data.

Conflicts of interest

Ban-An Khaw is a shareholder in Molecular Targeting Technologies, Inc. The other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. University of Oklahoma Health Sciences Center, Oklahoma, OK, USA

    Gerald Johnson III & Robert D. Okada

  2. University of Tulsa, 6208 S. Oswego Ave., Tulsa, OK, 74136, USA

    Gerald Johnson III & Robert D. Okada

  3. University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    David R. Okada

  4. University of Arizona School of Medicine, Tucson, AZ, USA

    Zhonglin Liu

  5. Oklahoma State University School of Medicine, Tulsa, OK, USA

    Delia Beju

  6. Northeastern University, Boston, MA, USA

    Ban An Khaw

Authors
  1. David R. Okada
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  2. Zhonglin Liu
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  3. Gerald Johnson III
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  4. Delia Beju
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  5. Ban An Khaw
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  6. Robert D. Okada
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Corresponding author

Correspondence to Robert D. Okada.

Additional information

This work was supported by the American Heart Association, the Anne and Henry Zarrow Foundation, and the William K. Warren Medical Research Foundation.

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Okada, D.R., Liu, Z., Johnson, G. et al. 99mTc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model. Eur J Nucl Med Mol Imaging 37, 1909–1917 (2010). https://doi.org/10.1007/s00259-010-1495-0

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  • DOI: https://doi.org/10.1007/s00259-010-1495-0

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