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Evaluation of 99  mTcN-MPO as a New Myocardial Perfusion Imaging Agent in Normal Dogs and in an Acute Myocardial Infarction Canine Model: Comparison with 99  mTc-Sestamibi

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Abstract

Purpose

99  mTcN-MPO ([99  mTcN(mpo)(PNP5)]+: mpo = 2-mercaptopyridine oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a cationic 99  mTc-nitrido complex, which has favorable biodistribution and myocardial uptake with rapid liver clearance in Sprague Dawley rats. The objective of this study was to compare the biodistribution and pharmacokinetics of 99  mTcN-MPO and 99  mTc-Sestamibi in normal dogs, and to evaluate the potential of 99  mTcN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction.

Methods

Five normal mongrel dogs were injected intravenously with 99  mTcN-MPO. Venous blood samples were collected via a femoral vein catheter at 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 60, and 90 min post-injection (p.i.). Anterior-posterior planar images were acquired by γ-camera at 10, 20, 30, 60, 90, and 120 min p.i. Regions of interest (ROIs) were drawn around the heart, liver, and lungs. The heart/liver and heart/lung ratios were calculated by dividing the mean counts in heart ROI by the mean counts in the liver and lung ROI, respectively. For comparison, 99  mTc-sestamibi was also evaluated in the same five dogs. The interval period between the two examinations was 1 week to eliminate possible interference between these two radiotracers. In addition, single positron emission computed tomography (SPECT) images in the canine infarct model were collected 24 h after myocardial infarction at 30 and 60 min after the administration of 99  mTcN-MPO (n = 4) or 99  mTc-Sestamibi (n = 4).

Results

It was found that 99  mTcN-MPO and 99  mTc-Sestamibi displayed very similar blood clearance characteristics during the first 90 min p.i. Both 99  mTcN-MPO and 99  mTc-Sestamibi had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min and less than 5% at 30 min p.i. 99  mTcN-MPO and 99  mTc-Sestamibi both showed good heart/lung contrast. The heart/liver ratio of 99  mTcN-MPO increased with time (0.53 ± 0.06 at 10 min, 0.90 ± 0.062 at 30 min, and 1.22 ± 0.06 at 60 min p.i.), whereas the heart/liver ratio of 99  mTc-Sestamibi remained low at all time points (0.50 ± 0.03 at 10 min, 0.64 ± 0.03 at 30 min, and 0.60 ± 0.02 at 60 min p.i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of 99  mTcN-MPO but not after 99  mTc-Sestamibi.

Conclusion

The combination of reasonable heart uptake with rapid hepatobiliary excretion makes 99  mTcN-MPO a promising new radiotracer for myocardial perfusion imaging.

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Acknowledgments

This work was supported, in part, by the following research grants: 2009DFB30040 from the international cooperation projects of the Chinese Ministry of Science and Technology, 20070420165 from the National Science Foundation for Postdoctoral Scientists of China, 2007AA3CS085 from the Science and Technology Tackle Key Problem Plan Foundation of Harbin. The authors wish to thank Drs. Fan Wang and Bing Jia from Peking University for technical support.

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Authors and Affiliations

  1. Department of Pharmacology, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, Heilongjiang, 150001, People’s Republic of China

    Lihong Bu, Baofeng Yang & Baozhong Shen

  2. Department of Medical Imaging, the Fourth Hospital of Harbin Medical University, 31 Yinhang Street, Nangang District, Harbin, Heilongjiang, 150001, People’s Republic of China

    Lihong Bu, Renfei Li, Zhongnan Jin, Xiaofei Wen & Baozhong Shen

  3. Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, Stanford, CA, 94305-5484, USA

    Lihong Bu & Xiaoyuan Chen

  4. School of Health Sciences, Purdue University, West Lafayette, IN, 47907-2036, USA

    Shuang Liu

  5. Laboratory for Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, MD, 20892-2281, USA

    Xiaoyuan Chen

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  1. Lihong Bu
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Correspondence to Baozhong Shen or Xiaoyuan Chen.

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Lihong Bu and Renfei Li contributed equally to this work

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Bu, L., Li, R., Jin, Z. et al. Evaluation of 99  mTcN-MPO as a New Myocardial Perfusion Imaging Agent in Normal Dogs and in an Acute Myocardial Infarction Canine Model: Comparison with 99  mTc-Sestamibi. Mol Imaging Biol 13, 121–127 (2011). https://doi.org/10.1007/s11307-010-0304-2

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