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In vivo molecular imaging of myocardial angiogenesis using the αvβ3 integrin-targeted tracer 99mTc-RAFT-RGD

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Myocardial angiogenesis following reperfusion of an infarcted area may impact on patient prognosis and pro-angiogenic treatments are currently evaluated. The non-invasive imaging of angiogenesis would therefore be of potential clinical relevance in these settings. 99mTc-RAFT-RGD is a novel 99mTc-labeled tracer that targets the αvβ3 integrin. Our objective was to determine whether this tracer was suitable for myocardial angiogenesis imaging.

Methods and Results

A rat model of reperfused myocardial infarction was employed. Fourteen days following reperfusion, the animals were injected with 99mTc-RAFT-RGD or with its negative control 99mTc-RAFT-RAD. Fourteen animals were dedicated to autoradiographic imaging, infarct staining, and gamma-well counting of myocardial activity. In vivo dual-isotope pinhole SPECT imaging of 201Tl and 99mTc-RAFT-RGD or 99mTc-RAFT-RAD was also performed in 11 additional animals. Neovessels were observed by immunostaining in the infarcted and peri-infarct areas. 99mTc-RAFT-RGD infarct-to-normal ratios by gamma-well counting and ex vivo imaging (2.5 ± 0.6 and 4.9 ± 0.9, respectively) were significantly higher than those of 99mTc-RAFT-RAD (1.7 ± 0.2 and 2.2 ± 0.4, respectively, P < .05). The infarcted area was readily visible in vivo by SPECT with 99mTc-RAFT-RGD but not with 99mTc-RAFT-RAD (infarct-to-normal zone activity ratio, 2.5 ± 0.6 and 1.7 ± 0.4, respectively, P < .05).

Conclusion

99mTc-RAFT-RGD allowed the experimental in vivo molecular imaging of myocardial angiogenesis.

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Authors and Affiliations

  1. INSERM U877, Radiopharmaceutiques Biocliniques, Faculté de Médecine de Grenoble, 38700, La Tronche, Grenoble, France

    Julien Dimastromatteo MS, Laurent M. Riou PhD, Mitra Ahmadi PharmD, Guillaume Pons MS, Eric Pellegrini PhD, Alexis Broisat PhD, Lucie Sancey PhD, Tatiana Gavrilina MD, Daniel Fagret MD, PhD & Catherine Ghezzi PhD

  2. Université Joseph Fourier, Grenoble, France

    Julien Dimastromatteo MS, Laurent M. Riou PhD, Mitra Ahmadi PharmD, Guillaume Pons MS, Eric Pellegrini PhD, Alexis Broisat PhD, Lucie Sancey PhD, Tatiana Gavrilina MD, Didier Boturyn PhD, Pascal Dumy PhD, Daniel Fagret MD, PhD & Catherine Ghezzi PhD

  3. Département de Chimie Moléculaire, CNRS, UMR-5250, Grenoble, France

    Didier Boturyn PhD & Pascal Dumy PhD

  4. ERAS Labo, Saint Nazaire les Eymes, France

    Julien Dimastromatteo MS

  5. Biospace Lab, Paris, France

    Eric Pellegrini PhD

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  1. Julien Dimastromatteo MS
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  2. Laurent M. Riou PhD
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Correspondence to Laurent M. Riou PhD.

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Funding

Financial support was provided by the National Institute for Health and Medical Research (INSERM), the National Agency for Research and technology (ANRT), and ERAS Labo. The authors have no conflict of interest to disclose.

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Dimastromatteo, J., Riou, L.M., Ahmadi, M. et al. In vivo molecular imaging of myocardial angiogenesis using the αvβ3 integrin-targeted tracer 99mTc-RAFT-RGD. J. Nucl. Cardiol. 17, 435–443 (2010). https://doi.org/10.1007/s12350-010-9191-9

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  • DOI: https://doi.org/10.1007/s12350-010-9191-9

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