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Mechanism for myocardial localization and rapid liver clearance of Tc-99m-N-MPO: A new perfusion radiotracer for heart imaging

Journal of Nuclear Cardiology volume 16, pages 571–579 (2009)Cite this article

Abstract

Background

[Tc-99m-N(mpo)(PNP5)]+ (Tc-99m-N-MPO: Hmpo = 2-mercaptopyridine N-oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a new Tc-99m radiotracer useful for myocardial perfusion imaging. The main objective of this study is to elucidate the mechanism for myocardial localization and fast liver clearance of Tc-99m-N-MPO in comparison with Tc-99m-sestamibi ([Tc-99m-(MIBI)6]+: MIBI = 2-methoxy-2-methylpropylisonitrile).

Methods and Results

Subcellular distribution of Tc-99m-N-MPO and Tc-99m-sestamibi was examined in the excised Sprague-Dawley (SD) rat myocardium. Biodistribution and planar imaging studies were performed using SD rats in the absence/presence of Cyclosporin-A. Due to negative plasma and mitochondrial potentials, 84.5% ± 3.2% of Tc-99m-N-MPO was found in the mitochondrial fraction as compared to 88.0% ± 1.5% of Tc-99m-sestamibi. There was no significant difference in their mitochondrial accumulation. Tc-99m-N-MPO was also able to retain its chemical integrity in rat myocardium. Pre-treatment of SD rats with Cys-A result in significant increase in the kidney and liver uptake of Tc-99m-N-MPO.

Conclusion

Tc-99m-N-MPO and Tc-99m-sestamibi share almost identical subcellular distribution and localization mechanism. The MDR transport function of hepatocytes and renal cells is responsible for the fast clearance kinetics of Tc-99m-N-MPO from liver and kidneys, respectively. Tc-99m-N-MPO is a very promising myocardial perfusion radiotracer with favorable biodistribution properties and rapid liver clearance.

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Acknowledgments

This work was supported, in part, by Purdue University and research grants: R01 CA115883 A2 (S.L.) from the National Cancer Institute (NCI), R21 EB003419-02 (S.L.) from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and R21 HL083961-01 from the National Heart, Lung, and Blood Institute (NHLBI).

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  1. Civil Engineering Building, School of Health Sciences, Purdue University, Room 1275, 550 Stadium Mall Drive, West Lafayette, IN, 47907, USA

    Young-Seung Kim PhD, Jiyun Shi MS, Shizhen Zhai MS, Guihua Hou MD, PhD & Shuang Liu PhD

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  1. Young-Seung Kim PhD
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Correspondence to Shuang Liu PhD.

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Kim, YS., Shi, J., Zhai, S. et al. Mechanism for myocardial localization and rapid liver clearance of Tc-99m-N-MPO: A new perfusion radiotracer for heart imaging. J. Nucl. Cardiol. 16, 571–579 (2009). https://doi.org/10.1007/s12350-009-9068-y

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Keywords

  • Cationic Tc-99m radiotracers
  • myocardial perfusion imaging
  • Tc-99m-N-MPO